{"id":12789,"date":"2026-02-19T18:18:00","date_gmt":"2026-02-19T18:18:00","guid":{"rendered":"https:\/\/csiag.de\/?p=12789"},"modified":"2026-02-21T06:07:24","modified_gmt":"2026-02-21T06:07:24","slug":"immune-cell-therapy","status":"publish","type":"post","link":"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/","title":{"rendered":"Immune cell therapy"},"content":{"rendered":"<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_83 counter-hierarchy ez-toc-counter ez-toc-grey ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">Table of contents<\/p>\n<span class=\"ez-toc-title-toggle\"><\/span><\/div>\n<nav><ul class='ez-toc-list ez-toc-list-level-1' ><ul class='ez-toc-list-level-2' ><li class='ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Das_Immunsystem_%E2%80%93_was_macht_das\" >The immune system - what does it do?<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Was_Immunzelltherapie_macht\" >What immune cell therapy does<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Das_Geniale_daran\" >The genius of it<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Die_drei_Typen_%E2%80%93_ganz_einfach\" >The three types - very simple<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-5\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#T-Zellen_und_ihre_Rolle\" >T cells and their role<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-6\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Tumorimmunologie-Grundprinzip\" >Tumor immunology basic principle<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-7\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#CAR-T-Zelltherapie_%E2%80%93_Konstruktion_und_Mechanismus\" >CAR-T cell therapy - design and mechanism<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-8\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Molekularer_Aufbau_des_CAR\" >Molecular structure of the CAR<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-9\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Herstellungsprozess_Autolog\" >Manufacturing process (Autolog)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-10\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Wirkmechanismus_Effektorphase\" >Mechanism of action &amp; effector phase<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-11\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#TCR-T-Zelltherapie_Die_entscheidenden_Unterschiede\" >TCR-T cell therapy: the key differences<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-12\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Warum_TCR_und_nicht_CAR_fur_intrazellulare_Antigene\" >Why TCR and not CAR for intracellular antigens?<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-13\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Struktur_des_therapeutischen_TCR\" >Structure of the therapeutic TCR<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-14\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#TIL-Therapie_%E2%80%93_Prinzip_der_naturlichen_Tumorerkennung\" >TIL therapy - principle of natural tumor detection<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-15\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Biologische_Grundlage\" >Biological basis<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-16\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Herstellungsprozess_Lifileucel\" >Manufacturing process (Lifileucel)<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-17\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Herausforderungen_%E2%80%93_aktuelle_Forschungsansatze\" >Challenges - current research approaches<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-18\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Antigen-Escape\" >Antigen escape<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-19\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#T-Zell-Erschopfung_Exhaustion\" >T-cell exhaustion (exhaustion)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-20\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Tumormikroumgebung_TME\" >Tumor microenvironment (TME)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-21\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Zytokinsturm_CRS_ICANS\" >Cytokine storm (CRS) &amp; ICANS<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-22\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Allogene_%E2%80%9EOff-the-shelf%E2%80%9C-Therapien\" >Allogeneic \u201eoff-the-shelf\u201c therapies<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-23\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#27_Quantitative_Wirksamkeitsdaten_im_Uberblick\" >2.7 Quantitative effectiveness data at a glance<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-24\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Weiterfuhrende_Literatur_Ressourcen\" >Further reading &amp; resources<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-25\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Weltweit_zugelassene_Immunzelltherapien\" >Globally approved immune cell therapies<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-26\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Einleitung_Die_drei_grosen_Klassen\" >Introduction: The three major classes<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-27\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#CAR-T-ZELLTHERAPIEN\" >CAR-T CELL THERAPIES<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-28\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Tisagenlecleucel_Kymriah%C2%AE_%E2%80%93_Novartis\" >Tisagenlecleucel (Kymriah\u00ae) - Novartis<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-29\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Axicabtagene_Ciloleucel_Yescarta%C2%AE_%E2%80%93_KiteGilead\" >Axicabtagene ciloleucel (Yescarta\u00ae) - Kite\/Gilead<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-30\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Brexucabtagene_Autoleucel_Tecartus%C2%AE_%E2%80%93_KiteGilead\" >Brexucabtagene Autoleucel (Tecartus\u00ae) - Kite\/Gilead<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-31\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Lisocabtagene_Maraleucel_Breyanzi%C2%AE_%E2%80%93_Bristol_Myers_Squibb\" >Lisocabtagene Maraleucel (Breyanzi\u00ae) - Bristol Myers Squibb<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-32\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Idecabtagene_Vicleucel_Abecma%C2%AE_%E2%80%93_Bristol_Myers_Squibb_2seventy_bio\" >Idecabtagene Vicleucel (Abecma\u00ae) - Bristol Myers Squibb \/ 2seventy bio<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-33\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Ciltacabtagene_Autoleucel_Carvykti%C2%AE_%E2%80%93_JanssenLegend_Biotech\" >Ciltacabtagene Autoleucel (Carvykti\u00ae) - Janssen\/Legend Biotech<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-34\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Obecabtagene_Autoleucel_Aucatzyl%C2%AE_%E2%80%93_Autolus_neu_112024\" >Obecabtagene Autoleucel (Aucatzyl\u00ae) - Autolus (new: 11.2024)<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-35\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#WELTWEIT_ZUGELASSEN_%E2%80%93_NICHT_IN_USAEU_weitere_Lander\" >ALLOWED WORLDWIDE - NOT IN USA\/EU (other countries)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-36\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#China_NMPA_%E2%80%93_vier_zusatzliche_CAR-T-Produkte\" >China (NMPA) - four additional CAR-T products<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-37\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Indien_CDSCO\" >India (CDSCO)<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-38\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#TCR-T-ZELLTHERAPIEN_zugelassen\" >TCR-T CELL THERAPIES (approved)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-39\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Afamitresgene_Autoleucel_Tecelra%C2%AE_%E2%80%93_Adaptimmune_August_2024\" >Afamitresgene Autoleucel (Tecelra\u00ae) - Adaptimmune (August 2024)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-40\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Tebentafusp-tebn_Kimmtrak%C2%AE_%E2%80%93_Immunocore_Januar_2022\" >Tebentafusp-tebn (Kimmtrak\u00ae) - Immunocore (January 2022)<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-41\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#TIL-THERAPIE_zugelassen\" >TIL-THERAPY (approved)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-42\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Lifileucel_Amtagvi%C2%AE_%E2%80%93_Iovance_Biotherapeutics_Februar_2024\" >Lifileucel (Amtagvi\u00ae) - Iovance Biotherapeutics (February 2024)<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-43\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Ubersicht_aller_Immunzelltherapien_weltweit\" >Overview of all immune cell therapies worldwide<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-44\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Nebenwirkungen_%E2%80%93_Was_alle_Therapien_verbindet\" >Side effects - what all therapies have in common<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-45\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Wo_werden_diese_Therapien_in_Deutschland_angeboten\" >Where are these therapies offered in Germany?<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-46\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Ausblick_Was_kommt_als_nachstes\" >Outlook: What's next?<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-1'><a class=\"ez-toc-link ez-toc-heading-47\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#GKV-Erstattung_von_Immunzelltherapien_in_Deutschland\" >SHI reimbursement of immune cell therapies in Germany<\/a><ul class='ez-toc-list-level-2' ><li class='ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-48\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#CAR-T-Zelltherapien\" >CAR-T cell therapies<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-49\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#AMNOG_NUB-Verfahren\" >AMNOG &amp; NUB procedure<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-50\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Fruhe_Nutzenbewertung_durch_den_G-BA\" >Early benefit assessment by the G-BA<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-51\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Preisverhandlung_nach_%C2%A7_130b_SGB_V\" >Price negotiation according to \u00a7 130b SGB V<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-52\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#NUB-Verfahren_fur_Krankenhauser\" >NUB procedure for hospitals<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-53\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Die_Realitat_Einzelfallantrage_und_Burokratie\" >The reality: individual applications and bureaucracy<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-54\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Das_%E2%80%9EPay-for-Outcome%E2%80%9C-Modell\" >The \u201epay-for-outcome\u201c model<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-55\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Welche_CAR-T-Produkte_sind_in_Deutschland_erstattungsfahig\" >Which CAR-T products are eligible for reimbursement in Germany?<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-56\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Kimmtrak_Tebentafusp_%E2%80%93_Sonderfall\" >Kimmtrak (Tebentafusp) - special case<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-57\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#TIL-Therapie_Lifileucel_Amtagvi_%E2%80%93_In_Deutschland_derzeit_NICHT_erstattungsfahig\" >TIL therapy (Lifileucel \/ Amtagvi) - Currently NOT reimbursable in Germany<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-58\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#TCR-T-Therapien_Afami-cel_Tecelra_%E2%80%93_In_Europa_nicht_zugelassen\" >TCR-T therapies (Afami-cel \/ Tecelra) - Not approved in Europe<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-59\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Was_tun_wenn_die_Kasse_ablehnt_Rechtliche_Moglichkeiten\" >What to do if the health insurance company refuses? Legal options<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-60\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Osterreich\" >Austria<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-61\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Schweiz\" >Switzerland<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-62\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Zusammenfassung\" >Summary<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-63\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#PKV_und_Immunzelltherapie_%E2%80%93_Die_vollstandige_Rechtslage\" >PKV and immune cell therapy - The complete legal situation<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-64\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Das_rechtliche_Fundament_%C2%A7_192_VVG_und_MBKK_2009\" >The legal foundation: \u00a7 192 VVG and MB\/KK 2009<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-65\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Der_Schlusselbegriff_%E2%80%9EMedizinisch_notwendige_Heilbehandlung%E2%80%9C\" >The key term: \u201eMedically necessary treatment\u201c<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-66\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Das_Richtungsurteil_OLG_Frankfurt_29062022_%E2%80%93_Az_7_U_14021\" >The landmark judgment: OLG Frankfurt, 29.06.2022 - Ref. 7 U 140\/21<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-67\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Das_%E2%80%9Eauffallige_Missverhaltnis%E2%80%9C_nach_%C2%A7_192_Abs_2_VVG_%E2%80%93_und_warum_es_bei_CAR-T_nicht_greift\" >The \u201econspicuous disproportion\u201c pursuant to Section 192 (2) VVG - and why it does not apply to CAR-T<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-68\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Das_Voranfrageverfahren_nach_%C2%A7_192_Abs_8_VVG_%E2%80%93_der_wichtigste_praktische_Schritt\" >The preliminary enquiry procedure in accordance with Section 192 (8) VVG - the most important practical step<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-69\" href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/#Bei_Ablehnung_Rechtsmittel_und_Klage\" >In case of rejection: appeal and legal action<\/a><\/li><\/ul><\/li><\/ul><\/li><\/ul><\/nav><\/div>\n<span class=\"span-reading-time rt-reading-time\" style=\"display: block;\"><span class=\"rt-label rt-prefix\">Reading time<\/span> <span class=\"rt-time\"> 20<\/span> <span class=\"rt-label rt-postfix\">minutes<\/span><\/span>\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Das_Immunsystem_%E2%80%93_was_macht_das\"><\/span>The immune system - what does it do?<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>The immune system maintains a whole army of scouts, fighters (<em>T-cells<\/em>) and helpers. They constantly patrol the body and search for intruders such as bacteria, viruses, but also the body's own cells that have gone wild - cancer cells.<\/p>\n\n\n\n<p>Normally, such rampaging cells are quickly detected by the guardians of the immune system, killed and their remains removed and decomposed. This happens continuously every day. In this way, most cancer cells are prevented from spreading by the immune system and are rendered harmless in good time.<\/p>\n\n\n\n<p>But cancer cells are inventive, as they want to survive at all costs. So they disguise themselves, hide effectively from the guardians of the immune system and continue to spread almost unchallenged. Not only do they make themselves unrecognizable as the enemy, they also keep the immune system so busy that after a certain time it becomes exhausted and may even have to stretch its wings - and succumb to the cancer.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Was_Immunzelltherapie_macht\"><\/span>What immune cell therapy does<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>In immune cell therapy, immune cells are removed from the patient, equipped with e.g. better recognition technology, more fighting power or a new \u201etarget optic\u201c and returned to the body, where they can attack and destroy the cancer in a more targeted manner.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Das_Geniale_daran\"><\/span>The genius of it<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Unlike chemotherapy, which in principle kills everything that divides quickly (cancer cells on the one hand, but also - unintentionally - hair cells, intestinal cells, etc.), immune cell therapies target <strong>only on cancer cells<\/strong> - at least in theory.<\/p>\n\n\n\n<p>As the immune system remembers enemies it has recognized, it immediately attacks the new cancer cells and destroys them should the cancer return. This explains why some patients remain permanently tumor-free after a single infusion.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Die_drei_Typen_%E2%80%93_ganz_einfach\"><\/span>The three types - very simple<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>1. CAR-T cells: The conversion<\/strong><br>T-cells (the immune system's combat troops) are taken and a completely new \u201egripper arm\u201c, an artificial receptor, is built into them in the laboratory. This recognizes a very specific feature on the surface of the cancer cell and then destroys the cancer cell directly.<\/p>\n\n\n\n<p><strong>2 TCR T cells: The better glasses<\/strong><br>Similar to CAR-T, instead of an artificial grasping arm, the T cell is given an improved natural receptor that also recognizes characteristics that are deeply <em>inside<\/em> of the cancer cell and only tiny fragments show to the outside.<\/p>\n\n\n\n<p><strong>3rd TIL therapy: The veteran<\/strong><br>Here, T cells are taken that are already <em>in the tumor itself<\/em> and know him. They are extracted, multiplied en masse in the laboratory - a few cells become billions - and sent back to experienced \u201eveterans\u201c.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"T-Zellen_und_ihre_Rolle\"><\/span>T cells and their role<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>The adaptive immune system is based on two main cell types: <strong>B cells<\/strong> (antibody production) and <strong>T-cells<\/strong> (cellular immunity). T cells, which are divided into two functional populations, are primarily relevant for all immune cell therapies:<\/p>\n\n\n\n<p><strong>CD8+ cytotoxic T cells (CTL)<\/strong><br>Recognize peptide-MHC class I complexes on the surface of infected or malignant cells via their T-cell receptor (TCR) and induce their apoptosis through perforin\/granzyme B release or FasL\/Fas interaction.<\/p>\n\n\n\n<p><strong>CD4+ helper T cells<\/strong><br>Coordinate the immune response via cytokine secretion (IL-2, IFN-\u03b3, TNF-\u03b1) and are essential for the long-term persistence of the CTL response.<\/p>\n\n\n\n<p><strong>Scientific basis:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Basic work on T-cell immunology: <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK10757\/\" target=\"_blank\" rel=\"noopener\">Janeway's Immunobiology (NCBI Bookshelf)<\/a><\/li>\n\n\n\n<li>Overview of T-cell exhaustion in cancer: <a href=\"https:\/\/www.nature.com\/articles\/nri3862\" target=\"_blank\" rel=\"noopener\">Wherry &amp; Kurachi, Nature Reviews Immunology 2015<\/a><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Tumorimmunologie-Grundprinzip\"><\/span>Tumor immunology basic principle<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Cancer does not develop in an immunological vacuum. The <strong>Cancer Immunoediting<\/strong>-concept (Dunn, Bruce &amp; Schreiber, 2004) describes three phases:<\/p>\n\n\n\n<p><strong>Elimination<\/strong><br>The immune system recognizes and destroys transformed cells via tumor-associated antigens (TAA) and tumor-specific antigens (TSA). MHC-I-mediated presentation of mutant peptides activates CTL.<\/p>\n\n\n\n<p><strong>Equilibrium<\/strong><br>The immune system keeps tumor growth in balance, but at the same time selects for immune-resistant variants.<\/p>\n\n\n\n<p><strong>Escape<\/strong><br>Cancer cells escape through downregulation of MHC-I, overexpression of immune checkpoints (PD-L1, CTLA-4 ligands), secretion of immunosuppressive cytokines (TGF-\u03b2, IL-10) and recruitment of regulatory T cells (Tregs).<\/p>\n\n\n\n<p><strong>Scientific basis:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/www.cell.com\/immunity\/fulltext\/S1074-7613(02)00272-3\" target=\"_blank\" rel=\"noopener\">Dunn et al, Immunity 2002<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/www.cell.com\/immunity\/fulltext\/S1074-7613(13)00272-X\" target=\"_blank\" rel=\"noopener\">Chen &amp; Mellman, Immunity 2013 - Cancer Immunity Cycle<\/a><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"CAR-T-Zelltherapie_%E2%80%93_Konstruktion_und_Mechanismus\"><\/span>CAR-T cell therapy - design and mechanism<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Molekularer_Aufbau_des_CAR\"><\/span>Molecular structure of the CAR<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>A chimeric antigen receptor (CAR) is a synthetic transmembrane protein with four functional domains:<\/p>\n\n\n\n<p><strong>1. extracellular binding domain<\/strong><br>Mostly a <strong>scFv<\/strong> (single-chain variable fragment) of a monoclonal antibody. Binds directly to a surface antigen (e.g. CD19 on B cells, BCMA on plasma cells) in an MHC-independent manner. This MHC-independence is a fundamental difference to the natural TCR.<\/p>\n\n\n\n<p><strong>2. hinge\/linker region<\/strong><br>Flexible spacer between binding domain and cell membrane (e.g. IgG4-Hinge, CD8\u03b1-Hinge). Length and flexibility strongly influence the binding efficiency.<\/p>\n\n\n\n<p><strong>3. transmembrane domain<\/strong><br>Anchors the CAR in the T cell membrane; influences signal stability.<\/p>\n\n\n\n<p><strong>4. intracellular signaling domain<\/strong><br>Consists of primary activation domain (CD3\u03b6 with 3 ITAMs) + co-stimulatory domains. The co-stimulatory domains define the <strong>CAR generation:<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Generation<\/th><th>Co-stimulation<\/th><th>Feature<\/th><\/tr><\/thead><tbody><tr><td>1st gen<\/td><td>CD3\u03b6 only<\/td><td>Short-lived, weak proliferation<\/td><\/tr><tr><td>2nd gen<\/td><td>CD28 <strong>or<\/strong> 4-1BB (CD137) + CD3\u03b6<\/td><td>Standard today; Kymriah=4-1BB; Yescarta=CD28<\/td><\/tr><tr><td>3rd gen<\/td><td>CD28 <strong>and<\/strong> 4-1BB + CD3\u03b6<\/td><td>Stronger activation, increased risk of CRS<\/td><\/tr><tr><td>4th gen<\/td><td>2nd gene + transgene (e.g. IL-12, IL-15)<\/td><td>\u201eArmored CAR\u201c, improved tumor microenvironment<\/td><\/tr><tr><td>5th gen<\/td><td>2nd gene + intracellular IL-2R\u03b2 domain<\/td><td>Jagged-CAR; JAK-STAT signaling pathway<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p><strong>4-1BB vs. CD28 co-stimulation<\/strong><br>4-1BB-CARs (Kymriah) show better long-term persistence and less exhaustion (less T-cell exhaustion), CD28-CARs (Yescarta) show faster initial activation and higher early response rates, but tend to have a shorter response duration.<\/p>\n\n\n\n<p><strong>Scientific basis:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Construction overview CAR: <a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMra1706169\" target=\"_blank\" rel=\"noopener\">June &amp; Sadelain, NEJM 2018<\/a><\/li>\n\n\n\n<li>4-1BB vs. CD28 comparison: <a href=\"https:\/\/www.nature.com\/articles\/s41591-018-0087-0\" target=\"_blank\" rel=\"noopener\">Salter et al, Nature Medicine 2018<\/a><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Herstellungsprozess_Autolog\"><\/span>Manufacturing process (Autolog)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p><strong>Leukapheresis<\/strong><br>The collection of mononuclear blood cells from the patient's blood via cell separation over 3-5 hours.<\/p>\n\n\n\n<p><strong>T-cell activation<\/strong><br>Ex vivo stimulation with anti-CD3\/anti-CD28 antibody-coated beads or recombinant ligands; addition of IL-2 and IL-7\/IL-15 to promote proliferation.<\/p>\n\n\n\n<p><strong>Gene transfer<\/strong><br>Introduction of the CAR gene by means of:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Lentiviral vector<\/strong> (Kymriah, Breyanzi): Stable integration into the host genome; long-term expression<\/li>\n\n\n\n<li><strong>Gammaretroviral vector<\/strong> (Yescarta, Tecartus): Similar, but higher insertional mutagenesis risk<\/li>\n\n\n\n<li><strong>Transposon systems \/ mRNA<\/strong> (experimental): Non-integrating alternatives<\/li>\n<\/ul>\n\n\n\n<p><strong>Expansion<\/strong><br>Multiplication of the transduced cells over 7-14 days to typically 10\u2078-10\u2079 cells.<\/p>\n\n\n\n<p><strong>Quality control<\/strong><br>Check for CAR transduction efficiency, sterility, residual components, T-cell phenotype, potency test.<\/p>\n\n\n\n<p><strong>Cryopreservation &amp; transportation<\/strong><br>to the treatment center.<\/p>\n\n\n\n<p><strong>Lymphodepletion<\/strong><br>Patient receives chemotherapy (usually fludarabine + cyclophosphamide) 2-7 days before CAR-T infusion to reduce the body's own immune cells and create \u201espace\u201c (lymphodepletive conditioning). This step massively increases the proliferation and persistence of CAR-T cells via homeostatic IL-7\/IL-15 signals.<\/p>\n\n\n\n<p><strong>Infusion<\/strong><br>Single intravenous infusion of CAR-T cells.<\/p>\n\n\n\n<p><strong>The science behind it:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Lymphodepletion mechanism: <a href=\"https:\/\/www.nature.com\/articles\/nm1263\" target=\"_blank\" rel=\"noopener\">Gattinoni et al, Nature Medicine 2005<\/a><\/li>\n\n\n\n<li>Production overview: <a href=\"https:\/\/www.cell.com\/molecular-therapy-family\/molecular-therapy\/fulltext\/S1525-0016(16)45462-1\" target=\"_blank\" rel=\"noopener\">Levine et al, Molecular Therapy 2017<\/a><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Wirkmechanismus_Effektorphase\"><\/span>Mechanism of action &amp; effector phase<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>After infusion, CAR-T cells recognize their target antigen on tumour cells, whereby an immunological synapse is formed: The CAR binds the antigen \u2192 CD3\u03b6-ITAMs are phosphorylated \u2192 ZAP-70\/Lck kinase cascade \u2192 NF-\u03baB, NFAT, AP-1 activation \u2192 perforin\/granzyme B release (direct cytolysis) + IFN-\u03b3, TNF-\u03b1 (cytokine secretion).<\/p>\n\n\n\n<p>Parallel: <strong>Bystander activation<\/strong> - released cytokines activate other endogenous immune cells and can lead to cytokine release syndrome (CRS).<\/p>\n\n\n\n<p><strong>Science:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>CAR-T mechanism of action: <a href=\"https:\/\/www.science.org\/doi\/10.1126\/science.aam8871\" target=\"_blank\" rel=\"noopener\">Lim &amp; June, Science 2017<\/a><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"TCR-T-Zelltherapie_Die_entscheidenden_Unterschiede\"><\/span>TCR-T cell therapy: the key differences<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Warum_TCR_und_nicht_CAR_fur_intrazellulare_Antigene\"><\/span>Why TCR and not CAR for intracellular antigens?<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>CAR receptors only recognize <strong>Surface proteins<\/strong>. However, since most tumor-specific antigens are localized intracellularly (transcription factors, metabolic enzymes, cancer testis antigens such as PRAME, MAGE-A4), CAR-T would be blind to these targets.<\/p>\n\n\n\n<p>The natural TCR has the ability to recognize intracellular proteins, as cellular proteins are constantly recognized by the <strong>Proteasome<\/strong> are degraded to ~8-11 amino acid long peptides. These peptides are degraded in the endoplasmic reticulum to <strong>MHC class I molecules (HLA in humans)<\/strong> and transported to the cell surface. There they are bound by the \u03b1\u03b2-TCR, a mechanism that is active on all nucleated body cells.<\/p>\n\n\n\n<p><strong>The technical challenge of TCR therapy<\/strong> is the necessary HLA restriction: a natural high-affinity TCR only recognizes a specific peptide in the context of a specific HLA allele (e.g. HLA-A*02:01, which occurs in approx. 40-50 % of the Caucasian population). This means that patients must be both HLA-compatible and tumor-positive for the target antigen.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Struktur_des_therapeutischen_TCR\"><\/span>Structure of the therapeutic TCR<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>Therapeutic TCRs are mostly <strong>\u03b1\u03b2-TCR heterodimers<\/strong>, which:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Developed through phage display or mouse humanization with extremely high affinity (KD in the pM range). The natural TCR has only medium affinity (\u03bcM), as too high affinity would lead to autoimmunity<\/li>\n\n\n\n<li>Stabilized against unintended pairing with endogenous TCR chains by murine substitutions or disulfide bridges<\/li>\n\n\n\n<li>be introduced into the patient's own T cells via lentiviral transduction<\/li>\n<\/ul>\n\n\n\n<p><strong>Science:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>TCR affinity engineering: <a href=\"https:\/\/www.jimmunol.org\/content\/180\/9\/6116\" target=\"_blank\" rel=\"noopener\">Robbins et al, Journal of Immunology 2008<\/a><\/li>\n\n\n\n<li>Mechanism overview TCR-T: <a href=\"https:\/\/aacrjournals.org\/cancerimmunolres\/article\/7\/8\/1236\/469286\" target=\"_blank\" rel=\"noopener\">Dangaj et al, Cancer Immunology Research 2019<\/a><\/li>\n\n\n\n<li>MAGE-A4 TCR base for Tecelra: <a href=\"https:\/\/aacrjournals.org\/clincancerres\/article\/25\/24\/7537\/82286\" target=\"_blank\" rel=\"noopener\">Kageyama et al, Clin Cancer Research 2019<\/a><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"TIL-Therapie_%E2%80%93_Prinzip_der_naturlichen_Tumorerkennung\"><\/span>TIL therapy - principle of natural tumor detection<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Biologische_Grundlage\"><\/span>Biological basis<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>Tumors are infiltrated by immune cells, the <strong>tumor-infiltrating lymphocytes (TIL)<\/strong>. These T cells have already recognized the tumour, but are often exhausted, anergic or too few due to the immunosuppressive tumour microenvironment (TME). High TIL density in the tumor correlates with a better prognosis in many types of cancer.<\/p>\n\n\n\n<p>The idea of TIL therapy (developed by Steven Rosenberg at the NCI, Bethesda, in the 1980s): Take these already tumor-specific T cells, free them from the immunosuppressive environment, activate and multiply them massively ex vivo, and return them in such large numbers that they become therapeutically effective despite a tendency to exhaustion.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Herstellungsprozess_Lifileucel\"><\/span>Manufacturing process (Lifileucel)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p><strong>Tumor excision<\/strong><br>At least 1.5 cm\u00b3 of tumor tissue is surgically removed and immediately processed into <a href=\"https:\/\/www.iovance.com\/\" target=\"_blank\" rel=\"noreferrer noopener\">Iovance Biotherapeutics, Inc.<\/a> sent.<\/p>\n\n\n\n<p><strong>Initial expansion (approx. 11 days)<\/strong><br>Tumor is mechanically and enzymatically dissociated; TIL are cultivated in the presence of IL-2 \u2192 Pre-REP (Pre-Rapid Expansion Protocol).<\/p>\n\n\n\n<p><strong>Rapid Expansion (approx. 11 days)<\/strong><br>TILs are treated with anti-CD3 antibodies (OKT3), irradiated allogeneic PBMCs (which act as antigen-presenting cells) and IL-2 on <strong>&gt;7.5 \u00d7 10\u2079 cells<\/strong> expands (from a few million to billions).<\/p>\n\n\n\n<p><strong>Lymphodepletion &amp; infusion<\/strong><br>Identical to CAR-T: Flu\/Cy conditioning, then single TIL infusion, followed by IL-2 administration for further in vivo expansion.<\/p>\n\n\n\n<p><strong>Time frame<\/strong><br>Approx. 22 days production; total from tumor removal to infusion approx. 6-7 weeks.<\/p>\n\n\n\n<p><strong>Science:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Rosenberg's pioneering work: <a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJM198812223192529\" target=\"_blank\" rel=\"noopener\">Rosenberg et al, NEJM 1988<\/a><\/li>\n\n\n\n<li>Lifileucel Phase 2 pivotal study (C-144-01): <a href=\"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.21.02179\" target=\"_blank\" rel=\"noopener\">Chesney et al, JCO 2022<\/a><\/li>\n\n\n\n<li>5-year follow-up: <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40699950\/\" target=\"_blank\" rel=\"noopener\">PubMed FDA Approval Summary 2024<\/a><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Herausforderungen_%E2%80%93_aktuelle_Forschungsansatze\"><\/span>Challenges - current research approaches<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Antigen-Escape\"><\/span>Antigen escape<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p><strong>Problem definition<\/strong><br>Tumor cells can downregulate or lose expression of the target antigen. In CD19-CAR-T, CD19-negative relapse occurs in 30-40 % of cases.<\/p>\n\n\n\n<p><strong>Solution<\/strong><br>Dual targeting strategies (CD19+CD22, BCMA+CD38), tandem CARs, logic gate CARs (AND gate: require two antigens; NOT gate: only kill cells without protective antigen).<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/www.nature.com\/articles\/nm.4164\" target=\"_blank\" rel=\"noopener\">Ruella et al, Nature Medicine 2016 (CD19-Escape)<\/a><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"T-Zell-Erschopfung_Exhaustion\"><\/span>T-cell exhaustion (exhaustion)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p><strong>Problem definition<\/strong><br>Tumor cells can downregulate or lose expression of the target antigen. In CD19-CAR-T, CD19-negative relapse occurs in 30-40 % of cases.<\/p>\n\n\n\n<p>Chronic antigen exposure \u2192 Expression of exhaustion markers (PD-1, TIM-3, LAG-3, TOX transcription factor) \u2192 Loss of function.<\/p>\n\n\n\n<p><strong>Solution:<\/strong> Combination with checkpoint inhibitors, epigenetic reprogramming via TET2 knockdown, next-gen CAR designs with built-in checkpoint blockade.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/www.nature.com\/articles\/s41586-019-1546-z\" target=\"_blank\" rel=\"noopener\">Chen et al, Nature 2019 (TET2 knockdown)<\/a><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Tumormikroumgebung_TME\"><\/span>Tumor microenvironment (TME)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p><strong>Problem definition<\/strong><br>Tumor cells can downregulate or lose expression of the target antigen. In CD19-CAR-T, CD19-negative relapse occurs in 30-40 % of cases.<\/p>\n\n\n\n<p>Solid tumors have a hostile microenvironment: hypoxia, glucose deficiency, immunosuppressive cytokines (TGF-\u03b2, IL-10), Tregs, MDSCs.<\/p>\n\n\n\n<p><strong>Solution<\/strong><br>Armored CARs with IL-12\/IL-15\/IL-18 secretion, PD-1-resistant CARs, combination with anti-VEGF, local intratumoral injections.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/www.nature.com\/articles\/s41598-017-10259-0\" target=\"_blank\" rel=\"noopener\">Yeku et al, Scientific Reports 2017 (Armored CAR)<\/a><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zytokinsturm_CRS_ICANS\"><\/span>Cytokine storm (CRS) &amp; ICANS<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p><strong>Problem definition<\/strong><br>CRS is caused by massive cytokine release (IL-6, IFN-\u03b3, IL-1\u03b2) of activated CAR-T and macrophages. Severe CRS (grade 3-4) requires intensive therapy. ICANS (neurological toxicity) results from endothelial activation and blood-brain barrier dysfunction.<\/p>\n\n\n\n<p><strong>Management<\/strong><br>Tocilizumab (IL-6R blockade), corticosteroids, anakinra (IL-1 blockade); early intervention improves results.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4116524\/\" target=\"_blank\" rel=\"noopener\">Lee et al, Blood 2014 - CRS grading system<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/www.nature.com\/articles\/nrneurol.2018.138\" target=\"_blank\" rel=\"noopener\">Neelapu et al, Nature Reviews Neurology 2018 - ICANS<\/a><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Allogene_%E2%80%9EOff-the-shelf%E2%80%9C-Therapien\"><\/span>Allogeneic \u201eoff-the-shelf\u201c therapies<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p><strong>Problem definition<\/strong><br>Tumor cells can downregulate or lose expression of the target antigen. In CD19-CAR-T, CD19-negative relapse occurs in 30-40 % of cases.<\/p>\n\n\n\n<p>Autologous production takes 3-6 weeks and is expensive (400,000-600,000 \u20ac).<\/p>\n\n\n\n<p><strong>Solution<\/strong><br>Allogeneic CAR-T from healthy donors, with CRISPR knockout of endogenous TCR (GvHD prevention) and HLA components (rejection prevention).<\/p>\n\n\n\n<p><strong>Current data<\/strong><br>CTX112 (CRISPR-allogeneic CD19-CAR-T) shows first complete remissions in CLL in phase 1.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/www.science.org\/doi\/10.1126\/science.abb4845\" target=\"_blank\" rel=\"noopener\">Stadtmauer et al, Science 2020 - CRISPR CAR-T Phase 1<\/a><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"27_Quantitative_Wirksamkeitsdaten_im_Uberblick\"><\/span>2.7 Quantitative effectiveness data at a glance<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Therapy<\/th><th>Indication<\/th><th>ORR<\/th><th>CR rate<\/th><th>Median OS<\/th><th>source<\/th><\/tr><\/thead><tbody><tr><td>Tisagenlecleucel<\/td><td>B-ALL pediatric<\/td><td>81 %<\/td><td>60 %<\/td><td>NR (63 % at 12 mo)<\/td><td>NEJM 2018<\/td><\/tr><tr><td>Axicabtagene-cel<\/td><td>DLBCL 3rd line<\/td><td>83 %<\/td><td>58 %<\/td><td>NR (74 % at 12 mo)<\/td><td>NEJM 2017<\/td><\/tr><tr><td>Ciltacabtagene-cel<\/td><td>Mult. myeloma<\/td><td>98 %<\/td><td>78 %<\/td><td>NR (&gt;80 % at 12 mo)<\/td><td>Lancet 2021<\/td><\/tr><tr><td>Lifileucel<\/td><td>Melanoma<\/td><td>31,4 %<\/td><td>7,5 %<\/td><td>NR (49 % at 24 mo)<\/td><td>JCO 2022<\/td><\/tr><tr><td>Afamitresgene-cel<\/td><td>Synovial sarcoma<\/td><td>43 %<\/td><td>4 %<\/td><td>16.4 months<\/td><td>Lancet 2024<\/td><\/tr><tr><td>Tebentafusp<\/td><td>Uveal melanoma<\/td><td>9 % (ORR)<\/td><td>&lt;1 %<\/td><td>21.7 months<\/td><td>NEJM 2021<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p><em>(NR = Not Reached; OS* not yet reached)<\/em><\/p>\n\n\n\n<p>*<em>O.S<\/em> (<em>Overall Survival<\/em>\u00a0) - e.g. \u201e<em>median OS 21.7<\/em>\u201e that half of the patients had died after 21.7 months and the other half were still alive<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Weiterfuhrende_Literatur_Ressourcen\"><\/span>Further reading &amp; resources<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>Reviews:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/www.science.org\/doi\/10.1126\/science.aar6711\" target=\"_blank\" rel=\"noopener\">June et al, Science 2018 - CAR-T therapy overview<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/link.springer.com\/article\/10.1007\/s00428-019-02571-3\" target=\"_blank\" rel=\"noopener\">Rohaan et al, Virchows Arch 2019 - TIL therapy review<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/www.nature.com\/articles\/s41586-019-1840-9\" target=\"_blank\" rel=\"noopener\">Stadtmauer et al, Nature 2020 - Allogeneic TCR\/CAR-T<\/a><\/li>\n<\/ul>\n\n\n\n<p><strong>Guidelines &amp; databases:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/clinicaltrials.gov\/search?term=CAR-T+OR+TIL+OR+TCR-T&amp;recency=5\" target=\"_blank\" rel=\"noopener\">ClinicalTrials.gov - all ongoing immune cell therapy trials<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/www.cancer.gov\/about-cancer\/treatment\/types\/immunotherapy\/t-cell-transfer-therapy\" target=\"_blank\" rel=\"noopener\">NCI - Immunotherapy overview<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/www.dgho.de\/informationen\/stellungnahmen\/gute-wissenschaftliche-praxis\/car-t-zellen\" target=\"_blank\" rel=\"noopener\">German Society for Hematology (DGHO) - CAR-T therapy<\/a><\/li>\n<\/ul>\n\n\n\n<p><strong>Patient-friendly resources (German):<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/www.krebshilfe.de\/informieren\/ueber-krebs\/therapie\/immuntherapie\/\" target=\"_blank\" rel=\"noopener\">Krebshilfe Deutschland - Immunotherapy explained<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/www.kitz-heidelberg.de\/forschungsprogramme\/zell-und-gentherapie\/\" target=\"_blank\" rel=\"noopener\">KiTZ Heidelberg - Patients &amp; Immunotherapy<\/a><\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<p><em>In less than a decade, immune cell therapy has made the leap from experimental concept to standard clinical therapy - with the number of approved products and indications continuing to grow rapidly. For patients who are eligible, it may be the only potentially curative option.<\/em><\/p>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Weltweit_zugelassene_Immunzelltherapien\"><\/span>Globally approved immune cell therapies<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>Status 02.2026<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Einleitung_Die_drei_grosen_Klassen\"><\/span>Introduction: The three major classes<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Today, the term \u201eimmune cell therapy\u201c covers three different product categories in the oncological context:<\/p>\n\n\n\n<p><strong>1. CAR-T cell therapy<\/strong> (Chimeric Antigen Receptor T-Cells)<br>Genetically modified T cells with a synthetic surface receptor that recognizes tumour antigens on the cell surface. All products approved to date are directed against CD19 or BCMA and are approved for blood cancers.<\/p>\n\n\n\n<p><strong>2. TCR-T cell therapy<\/strong> (T-Cell Receptor T-Cells)<br>Genetically modified T cells with an optimized natural T cell receptor that recognizes intracellular tumour proteins presented on the HLA complex. First approved for solid tumors in 2024.<\/p>\n\n\n\n<p><strong>3rd TIL therapy<\/strong> (Tumor-Infiltrating Lymphocytes)<br>Non-genetically modified T cells obtained from the patient's tumor, massively multiplied and reinfused. First approved for melanoma in 2024.<\/p>\n\n\n\n<p>As of December 2024, the FDA had approved six CAR-T cell therapies, with ten CAR-T cell therapies commercially available worldwide. In addition, there is a TIL therapy (Lifileucel) and a TCR therapy (Afamitresgene autoleucel) - the first in their class for solid tumors. <a href=\"https:\/\/www.curemelanoma.org\/blog\/melanoma-clinical-trials-to-watch-fall-2025\" target=\"_blank\" rel=\"noreferrer noopener\">MRA<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"CAR-T-ZELLTHERAPIEN\"><\/span>CAR-T CELL THERAPIES<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Tisagenlecleucel_Kymriah%C2%AE_%E2%80%93_Novartis\"><\/span>Tisagenlecleucel (Kymriah\u00ae) - <em>Novartis<\/em><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>Target antigen:<\/strong> CD19 <br><strong>Approved:<\/strong> FDA 2017 \/ EMA 2018<br><strong>First CAR-T product ever approved worldwide<\/strong><\/p>\n\n\n\n<p><strong>Indications<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Children &amp; young adults up to 25 years: relapsed\/refractory B-cell ALL (acute lymphoblastic leukemia)<\/li>\n\n\n\n<li>Adults: relapsed\/refractory large B-cell lymphoma (LBCL) after \u22652 systemic therapies<\/li>\n\n\n\n<li>Relapsed\/refractory follicular lymphoma (FL)<\/li>\n<\/ul>\n\n\n\n<p><strong>Most important studies<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>ELIANA study (ALL pediatric): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT02435849\" target=\"_blank\" rel=\"noopener\">NCT02435849<\/a> | <a href=\"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.21.01019\" target=\"_blank\" rel=\"noopener\">JCO 2021<\/a><\/li>\n\n\n\n<li>JULIET study (LBCL): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT02445248\" target=\"_blank\" rel=\"noopener\">NCT02445248<\/a><\/li>\n<\/ul>\n\n\n\n<p><strong>Regulatory authorities<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>FDA<\/li>\n\n\n\n<li>EMA<\/li>\n\n\n\n<li>TGA (Australia)<\/li>\n\n\n\n<li>PMDA (Japan) <\/li>\n<\/ul>\n\n\n\n<p><strong>Manufacturer\/Website:<\/strong> <a href=\"https:\/\/www.novartis.com\/us-en\/sites\/novartis_us\/files\/kymriah.pdf\" target=\"_blank\" rel=\"noopener\">Novartis Kymriah<\/a><\/p>\n\n\n\n<p><strong>FDA product page:<\/strong> <a href=\"https:\/\/www.fda.gov\/vaccines-blood-biologics\/kymriah\" target=\"_blank\" rel=\"noopener\">FDA Kymriah<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Axicabtagene_Ciloleucel_Yescarta%C2%AE_%E2%80%93_KiteGilead\"><\/span>Axicabtagene Ciloleucel (Yescarta\u00ae) - <em>Kite\/Gilead<\/em><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>Target antigen:<\/strong> CD19<br><strong>Approved:<\/strong> FDA October 2017 \/ EMA August 2018<\/p>\n\n\n\n<p><strong>Indications<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Large B-cell lymphoma (DLBCL, PMBCL, HGBCL, tFL) after \u22652 systemic therapies<\/li>\n\n\n\n<li>Primary refractory DLBCL or relapse within 12 months (2nd line)<\/li>\n\n\n\n<li>Relapsed\/refractory follicular lymphoma after \u22652 systemic therapies<\/li>\n<\/ul>\n\n\n\n<p><strong>Most important studies<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>ZUMA-1 (LBCL, ORR 82 %): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT02348216\" target=\"_blank\" rel=\"noopener\">NCT02348216<\/a> | <a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa1707447\" target=\"_blank\" rel=\"noopener\">NEJM 2017<\/a><\/li>\n\n\n\n<li>ZUMA-7 (2nd-line vs. ASCT): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT03391466\" target=\"_blank\" rel=\"noopener\">NCT03391466<\/a><\/li>\n\n\n\n<li>ZUMA-5 (follicular lymphoma, ORR &gt;90 %): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT03105336\" target=\"_blank\" rel=\"noopener\">NCT03105336<\/a><\/li>\n<\/ul>\n\n\n\n<p><strong>Treatment centers (D\/A\/CH selection)<\/strong><\/p>\n\n\n\n<p>All qualified FACT\/JACIE-accredited transplant centers; in Germany e.g. University Medical Center Hamburg-Eppendorf, Charit\u00e9 Berlin, LMU Klinikum M\u00fcnchen, University Medical Center Heidelberg.<\/p>\n\n\n\n<p><strong>Manufacturer\/Website<\/strong>: <a href=\"https:\/\/www.yescarta.com\" target=\"_blank\" rel=\"noopener\">Gilead Yescarta<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Brexucabtagene_Autoleucel_Tecartus%C2%AE_%E2%80%93_KiteGilead\"><\/span>Brexucabtagene Autoleucel (Tecartus\u00ae) - <em>Kite\/Gilead<\/em><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>Target antigen:<\/strong> CD19<br><strong>Approved:<\/strong> FDA July 2020 (MCL), October 2021 (ALL adult) \/ EMA December 2020<\/p>\n\n\n\n<p><strong>Indications<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Relapsed\/refractory mantle cell lymphoma (MCL) after BTK inhibitor<\/li>\n\n\n\n<li>Adults with relapsed\/refractory B-cell ALL<\/li>\n<\/ul>\n\n\n\n<p><strong>Most important studies<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>ZUMA-2 (MCL, OS 12 months: 83 %): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT02601313\" target=\"_blank\" rel=\"noopener\">NCT02601313<\/a><\/li>\n\n\n\n<li>ZUMA-3 (adult B-ALL, median OS 18.2 months): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT02614066\" target=\"_blank\" rel=\"noopener\">NCT02614066<\/a><\/li>\n<\/ul>\n\n\n\n<p><strong>FDA product page:<\/strong> <a href=\"https:\/\/www.fda.gov\/vaccines-blood-biologics\/tecartus\" target=\"_blank\" rel=\"noopener\">FDA Tecartus<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Lisocabtagene_Maraleucel_Breyanzi%C2%AE_%E2%80%93_Bristol_Myers_Squibb\"><\/span>Lisocabtagene Maraleucel (Breyanzi\u00ae) - <em>Bristol Myers Squibb<\/em><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>Target antigen:<\/strong> CD19<br><strong>Approved:<\/strong> FDA February 2021 (initial) \/ extended indications 2022-2024 \/ EMA October 2022<\/p>\n\n\n\n<p><strong>Indications<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Large B-cell lymphoma (LBCL, DLBCL, HGBCL, FL) 2nd + 3rd lineage<\/li>\n\n\n\n<li>Chronic lymphocytic leukemia (CLL) \/ small cell lymphocytic lymphoma (SLL) after \u22652 therapies incl. BTK inhibitor (FDA 2024)<\/li>\n\n\n\n<li>Follicular lymphoma (FL) after \u22652 systemic therapies<\/li>\n<\/ul>\n\n\n\n<p><strong>Most important studies<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>TRANSFORM (2nd-line DLBCL): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT03575351\" target=\"_blank\" rel=\"noopener\">NCT03575351<\/a><\/li>\n\n\n\n<li>TRANSCEND-CLL-004 (CLL\/SLL): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT03331198\" target=\"_blank\" rel=\"noopener\">NCT03331198<\/a> | <a href=\"https:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736(24)00422-7\/fulltext\" target=\"_blank\" rel=\"noopener\">Lancet 2024<\/a><\/li>\n<\/ul>\n\n\n\n<p><strong>FDA product page:<\/strong> <a href=\"https:\/\/www.fda.gov\/vaccines-blood-biologics\/breyanzi\" target=\"_blank\" rel=\"noopener\">FDA Breyanzi<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Idecabtagene_Vicleucel_Abecma%C2%AE_%E2%80%93_Bristol_Myers_Squibb_2seventy_bio\"><\/span>Idecabtagene Vicleucel (Abecma\u00ae) - <em>Bristol Myers Squibb \/ 2seventy bio<\/em><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>Target antigen:<\/strong> BCMA (B-cell maturation antigen)<br><strong>Approved:<\/strong> FDA March 2021 \/ EMA August 2021<\/p>\n\n\n\n<p><strong>Indication<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Relapsed\/refractory multiple myeloma after \u22654 previous lines of therapy<\/li>\n<\/ul>\n\n\n\n<p><strong>Most important study<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>KarMMa study (ORR 73 %): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT03361748\" target=\"_blank\" rel=\"noopener\">NCT03361748<\/a> | <a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa2024850\" target=\"_blank\" rel=\"noopener\">NEJM 2021<\/a><\/li>\n<\/ul>\n\n\n\n<p><strong>FDA product page:<\/strong> <a href=\"https:\/\/www.fda.gov\/vaccines-blood-biologics\/abecma\" target=\"_blank\" rel=\"noopener\">FDA Abecma<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ciltacabtagene_Autoleucel_Carvykti%C2%AE_%E2%80%93_JanssenLegend_Biotech\"><\/span>Ciltacabtagene Autoleucel (Carvykti\u00ae) - <em>Janssen\/Legend Biotech<\/em><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>Target antigen:<\/strong> BCMA (dual-binding)<br><strong>Approved:<\/strong> FDA February 2022 (\u22654 lines), extended April 2024 (\u22651 line) \/ EMA May 2022<\/p>\n\n\n\n<p><strong>Special feature:<\/strong> Unique dual-antibody CAR with two BCMA-binding single-domain antibodies; considered the most effective approved myeloma therapy to date<\/p>\n\n\n\n<p><strong>Indications<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Relapsed\/refractory multiple myeloma after \u22654 lines of therapy<\/li>\n\n\n\n<li>Since April 2024 (FDA): after \u22651 line of therapy for lenalidomide-refractory disease<\/li>\n<\/ul>\n\n\n\n<p><strong>Most important studies<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>CARTITUDE-1 (ORR 98 %, CR 78 %): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT03548207\" target=\"_blank\" rel=\"noopener\">NCT03548207<\/a> | <a href=\"https:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736(21)00933-4\/fulltext\" target=\"_blank\" rel=\"noopener\">Lancet 2021<\/a><\/li>\n\n\n\n<li>CARTITUDE-4 (Phase 3, extension of 1st relapse): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT04181827\" target=\"_blank\" rel=\"noopener\">NCT04181827<\/a><\/li>\n<\/ul>\n\n\n\n<p><strong>FDA product page:<\/strong> <a href=\"https:\/\/www.fda.gov\/vaccines-blood-biologics\/carvykti\" target=\"_blank\" rel=\"noopener\">FDA Carvykti<\/a><br><strong>Manufacturer:<\/strong> <a href=\"https:\/\/www.carvykti.com\" target=\"_blank\" rel=\"noopener\">carvykti.com<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Obecabtagene_Autoleucel_Aucatzyl%C2%AE_%E2%80%93_Autolus_neu_112024\"><\/span>Obecabtagene Autoleucel (Aucatzyl\u00ae) - <em>Autolus<\/em> <em>(new: 11.2024)<\/em><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>Target antigen:<\/strong> CD19 (fast-off-rate design - lower toxicity than predecessor)<br><strong>Approved:<\/strong> FDA November 8, 2024<\/p>\n\n\n\n<p><strong>Indication<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Adults with relapsed\/refractory B-cell ALL<\/li>\n<\/ul>\n\n\n\n<p><strong>Special feature:<\/strong> First CAR-T product approved without REMS (Risk Evaluation and Mitigation Strategy) program; a sign of improved safety and a novel CD19 binding concept.<br><a href=\"https:\/\/www.dasgelbeblatt.de\/welt\/immunzelltherapie-heilt-ueberraschend-krebs-bei-einem-jugendlichen-zr-94168662.html\" target=\"_blank\" rel=\"noreferrer noopener\">The yellow sheet<\/a><\/p>\n\n\n\n<p><strong>Most important study<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>FELIX study (phase 1\/2, CR rate 42 % in 3 months): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT04404660\" target=\"_blank\" rel=\"noopener\">NCT04404660<\/a><\/li>\n<\/ul>\n\n\n\n<p><strong>FDA product page:<\/strong> <a href=\"https:\/\/www.fda.gov\/vaccines-blood-biologics\/aucatzyl\" target=\"_blank\" rel=\"noopener\">FDA Aucatzyl<\/a><br><strong>Manufacturer:<\/strong> <a href=\"https:\/\/www.autolus.com\" target=\"_blank\" rel=\"noopener\">autolus.com<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"WELTWEIT_ZUGELASSEN_%E2%80%93_NICHT_IN_USAEU_weitere_Lander\"><\/span>ALLOWED WORLDWIDE - NOT IN USA\/EU (other countries)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"China_NMPA_%E2%80%93_vier_zusatzliche_CAR-T-Produkte\"><\/span>China (NMPA) - four additional CAR-T products<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>A total of eleven autologous CAR-T cell therapies have received initial approval worldwide. Seven by the FDA and four by the Chinese NMPA, all for relapsed\/refractory hematologic malignancies.<br><a href=\"https:\/\/ucla.clinicaltrials.researcherprofiles.org\/trial\/NCT06743126\" target=\"_blank\" rel=\"noreferrer noopener\">Immatics US, Inc.<\/a><\/p>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Trade name<\/th><th>Active ingredient<\/th><th>Target antigen<\/th><th>Indication<\/th><th>Authorization<\/th><\/tr><\/thead><tbody><tr><td>Carteyva<\/td><td>Relmacabtagene autoleucel<\/td><td>BCMA<\/td><td>Mult. Myeloma, DLBCL<\/td><td>NMPA 2021\/2023<\/td><\/tr><tr><td>Fucaso<\/td><td>Equecabtagene autoleucel<\/td><td>BCMA<\/td><td>Mult. myeloma<\/td><td>NMPA 2023<\/td><\/tr><tr><td>Yuanruida<\/td><td>Satricabtagene autoleucel<\/td><td>CD19<\/td><td>B-cell lymphoma<\/td><td>NMPA<\/td><\/tr><tr><td>Zever-cel<\/td><td>\u2014<\/td><td>CD19\/BCMA<\/td><td>Hematolog.<\/td><td>NMPA<\/td><\/tr><tr><td>Carvykti<\/td><td>Ciltacabtagene autoleucel<\/td><td>BCMA<\/td><td>Mult. myeloma<\/td><td>NMPA 2024<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Indien_CDSCO\"><\/span>India (CDSCO)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>NexCAR19<\/strong> (Actalycabtagene autoleucel) was approved in October 2023 as the first CAR-T therapy developed in India. Developed by ImmunoACT at IIT Bombay, the therapy costs around USD 50,000 - around a tenth of comparable Western products. <a href=\"https:\/\/www.dasgelbeblatt.de\/welt\/immunzelltherapie-heilt-ueberraschend-krebs-bei-einem-jugendlichen-zr-94168662.html\" target=\"_blank\" rel=\"noreferrer noopener\">The yellow sheet<\/a><\/p>\n\n\n\n<p><strong>Indication<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Relapsed\/refractory B-cell non-Hodgkin's lymphoma and B-cell ALL<\/li>\n<\/ul>\n\n\n\n<p><strong>Treatment center:<\/strong> Tata Memorial Hospital, Mumbai <br><strong>Manufacturer:<\/strong> <a href=\"https:\/\/www.immunoact.com\" target=\"_blank\" rel=\"noopener\">ImmunoACT<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"TCR-T-ZELLTHERAPIEN_zugelassen\"><\/span>TCR-T CELL THERAPIES (approved)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Afamitresgene_Autoleucel_Tecelra%C2%AE_%E2%80%93_Adaptimmune_August_2024\"><\/span>Afamitresgene Autoleucel (Tecelra\u00ae) - <em>Adaptimmune<\/em> <em>(August 2024)<\/em><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>On August 2, 2024, the FDA approved Afamitresgene autoleucel (Afami-cel, Tecelra) as the first ever TCR T-cell therapy for the treatment of cancer and specifically the first genetically engineered T-cell product for a solid tumor. <a href=\"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC12283372\/\" target=\"_blank\" rel=\"noreferrer noopener\">PubMed Central<\/a><\/p>\n\n\n\n<p><strong>Target antigen:<\/strong> MAGE-A4 (intracellular cancer testis antigen), presented by HLA-A*02:01<br><strong>Approved:<\/strong> FDA August 2024<\/p>\n\n\n\n<p><strong>Indication<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Adults with unresectable or metastatic cancer <strong>Synovial sarcoma<\/strong> (soft tissue sarcoma), pre-treated with chemotherapy, MAGE-A4-positive and HLA-A*02:01-positive<\/li>\n<\/ul>\n\n\n\n<p>In the pivotal Phase 2 SPEARHEAD-1 trial, the tumors of synovial sarcoma patients responded to treatment for a median of 11.6 months. In some patients, no tumor could be detected for several years. <a href=\"https:\/\/www.clinicaltrialvanguard.com\/news\/t-knife-files-for-phase-1-trial-of-prame-t-cell-therapy\/\" target=\"_blank\" rel=\"noreferrer noopener\">Clinicaltrialvanguard<\/a><\/p>\n\n\n\n<p><strong>Most important study<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>SPEARHEAD-1 (Phase 2): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT04044858\" target=\"_blank\" rel=\"noopener\">NCT04044858<\/a> | <a href=\"https:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736(24)00319-2\/fulltext\" target=\"_blank\" rel=\"noopener\">Lancet April 2024<\/a><\/li>\n<\/ul>\n\n\n\n<p><strong>Treatment center (Pioneer):<\/strong> Memorial Sloan Kettering Cancer Center, New York - <a href=\"https:\/\/www.mskcc.org\/news\/immunotherapy-clinical-trial-shows-promise-for-treating-rare-sarcomas\" target=\"_blank\" rel=\"noopener\">MSK Tecelra Info<\/a><br><strong>FDA product page:<\/strong> <a href=\"https:\/\/www.fda.gov\/vaccines-blood-biologics\/tecelra\" target=\"_blank\" rel=\"noopener\">FDA Tecelra<\/a> <br><strong>NCI article:<\/strong> <a href=\"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2024\/fda-tecelra-synovial-sarcoma-mage-a4\" target=\"_blank\" rel=\"noopener\">cancer.gov TCR therapy<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Tebentafusp-tebn_Kimmtrak%C2%AE_%E2%80%93_Immunocore_Januar_2022\"><\/span>Tebentafusp-tebn (Kimmtrak\u00ae) - <em>Immunocore<\/em> <em>(January 2022)<\/em><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Not a classical cell product (not an infused T-cell product), but a bispecific TCR fusion protein, but mechanistically in the category of TCR-based immunotherapy and often discussed as a precursor of the PRAME-TCER\u00ae technology.<\/p>\n\n\n\n<p><strong>Mechanism:<\/strong> Binds on one side to gp100 peptide+HLA-A*02:01 on tumor cells, on the other to CD3 on T cells (ImmTAC technology).<br><strong>Approved:<\/strong> FDA January 2022 \/ EMA February 2022<\/p>\n\n\n\n<p><strong>Indication:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>HLA-A*02:01-positive adults with unresectable or metastatic cancer <strong>uveal melanoma<\/strong> (ocular melanoma) - 1st line<\/li>\n<\/ul>\n\n\n\n<p><strong>Special feature:<\/strong> First drug ever approved for uveal melanoma<\/p>\n\n\n\n<p>In the phase 3 IMCgp100-202 study, tebentafusp showed a significant survival advantage over physician's choice (pembrolizumab, ipilimumab or dacarbazine): median OS 21.7 vs. 16.0 months (HR 0.51; p&lt;0.0001). The 1-year OS rate was 73 % vs. 59 %. <a href=\"https:\/\/www.kitz-heidelberg.de\/das-kitz\/kitz-programme\/\" target=\"_blank\" rel=\"noreferrer noopener\">Kitz-heidelberg<\/a><\/p>\n\n\n\n<p><strong>Most important study<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>IMCgp100-202 (Phase 3): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT03070392\" target=\"_blank\" rel=\"noopener\">NCT03070392<\/a> | <a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa2103485\" target=\"_blank\" rel=\"noopener\">NEJM 2021<\/a> | <a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa2304753\" target=\"_blank\" rel=\"noopener\">3-year update NEJM 2023<\/a><\/li>\n<\/ul>\n\n\n\n<p><strong>FDA page:<\/strong> <a href=\"https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-disco-burst-edition-fda-approves-tebentafusp-tebn-unresectable-or-metastatic-uveal-melanoma\" target=\"_blank\" rel=\"noopener\">fda.gov Kimmtrak<\/a> <br><strong>Manufacturer:<\/strong> <a href=\"https:\/\/www.immunocore.com\/pipeline\/kimmtrak\" target=\"_blank\" rel=\"noopener\">immunocore.com\/kimmtrak<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"TIL-THERAPIE_zugelassen\"><\/span>TIL-THERAPY (approved)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Lifileucel_Amtagvi%C2%AE_%E2%80%93_Iovance_Biotherapeutics_Februar_2024\"><\/span>Lifileucel (Amtagvi\u00ae) - <em>Iovance Biotherapeutics<\/em> <em>(February 2024)<\/em><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Lifileucel was approved on February 16, 2024 as the first ever T-cell therapy for a solid tumor and the first TIL therapy in history. <a href=\"https:\/\/investors.immatics.com\/news-releases\/news-release-details\/immatics-initiates-phase-12-clinical-trial-evaluate-prame-tcr\/\" target=\"_blank\" rel=\"noreferrer noopener\">Immatics N.V.<\/a><\/p>\n\n\n\n<p><strong>Mechanism:<\/strong> Tumor is surgically removed, tumor-infiltrating lymphocytes (TIL) are isolated, massively multiplied and reinfused after lymphodepletion. No genetic modification - the natural tumor recognition of the TIL is used.<\/p>\n\n\n\n<p><strong>Indication<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Adults with unresectable or metastatic cancer <strong>Melanoma<\/strong> (cutaneous melanoma) after prior anti-PD-1 therapy and BRAF\/MEK inhibitor (if BRAF-mutated)<\/li>\n<\/ul>\n\n\n\n<p>In the 5-year follow-up of the Phase 2 C-144-01 study, Lifileucel demonstrated an objective response rate of 31.4 % and a median duration of response of 36.5 months - with sustained long-term responses in over 30 % responders. <a href=\"https:\/\/dailyreporter.esmo.org\/esmo-immuno-oncology-congress-2025\/news\/next-generation-prame-directed-tcr-t-cell-therapy-shows-early-activity-in-solid-tumours\" target=\"_blank\" rel=\"noreferrer noopener\">Esmo<\/a><\/p>\n\n\n\n<p><strong>Most important study<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>C-144-01 (Phase 2, NCT02360579): <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT02360579\" target=\"_blank\" rel=\"noopener\">ClinicalTrials<\/a> | <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40699950\/\" target=\"_blank\" rel=\"noopener\">FDA Approval Summary PubMed<\/a><\/li>\n<\/ul>\n\n\n\n<p><strong>Treatment centers (USA selection):<\/strong> Johns Hopkins, UCLA, MD Anderson, UCSF, Memorial Sloan Kettering, Mayo Clinic<br><strong>NCI article:<\/strong> <a href=\"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2024\/fda-amtagvi-til-therapy-melanoma\" target=\"_blank\" rel=\"noopener\">cancer.gov TIL therapy<\/a><br><strong>Manufacturer:<\/strong> <a href=\"https:\/\/www.iovance.com\" target=\"_blank\" rel=\"noopener\">iovance.com<\/a><br><strong>FDA product page:<\/strong> <a href=\"https:\/\/www.fda.gov\/vaccines-blood-biologics\/amtagvi\" target=\"_blank\" rel=\"noopener\">FDA Amtagvi<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ubersicht_aller_Immunzelltherapien_weltweit\"><\/span>Overview of all immune cell therapies worldwide<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Product<\/th><th>Active ingredient<\/th><th>Type<\/th><th>Goal<\/th><th>Indication<\/th><th>Authorization<\/th><th>Year<\/th><\/tr><\/thead><tbody><tr><td><strong>Kymriah<\/strong><\/td><td>Tisagenlecleucel<\/td><td>CAR-T<\/td><td>CD19<\/td><td>B-ALL pediatric, LBCL, FL<\/td><td>FDA, EMA<\/td><td>2017<\/td><\/tr><tr><td><strong>Yescarta<\/strong><\/td><td>Axicabtagene-cel<\/td><td>CAR-T<\/td><td>CD19<\/td><td>DLBCL, PMBCL, FL, tFL<\/td><td>FDA, EMA<\/td><td>2017<\/td><\/tr><tr><td><strong>Tecartus<\/strong><\/td><td>Brexucabtagene-cel<\/td><td>CAR-T<\/td><td>CD19<\/td><td>MCL, adult B-ALL<\/td><td>FDA, EMA<\/td><td>2020<\/td><\/tr><tr><td><strong>Breyanzi<\/strong><\/td><td>Lisocabtagene-cel<\/td><td>CAR-T<\/td><td>CD19<\/td><td>LBCL, CLL\/SLL, FL<\/td><td>FDA, EMA<\/td><td>2021<\/td><\/tr><tr><td><strong>Abecma<\/strong><\/td><td>Idecabtagene-cel<\/td><td>CAR-T<\/td><td>BCMA<\/td><td>Mult. Myeloma \u22654 lines<\/td><td>FDA, EMA<\/td><td>2021<\/td><\/tr><tr><td><strong>Carvykti<\/strong><\/td><td>Ciltacabtagene-cel<\/td><td>CAR-T<\/td><td>BCMA<\/td><td>Mult. Myeloma \u22651 line<\/td><td>FDA, EMA, NMPA<\/td><td>2022<\/td><\/tr><tr><td><strong>Kimmtrak<\/strong><\/td><td>Tebentafusp-tebn<\/td><td>TCR-Bispecific<\/td><td>gp100+HLA<\/td><td>Uveal melanoma<\/td><td>FDA, EMA<\/td><td>2022<\/td><\/tr><tr><td><strong>NexCAR19<\/strong><\/td><td>Actalycabtagene-cel<\/td><td>CAR-T<\/td><td>CD19<\/td><td>B-ALL, NHL<\/td><td>CDSCO (India)<\/td><td>2023<\/td><\/tr><tr><td><strong>Amtagvi<\/strong><\/td><td>Lifileucel<\/td><td>TIL<\/td><td>Polyclonal<\/td><td>Melanoma (solid tumor)<\/td><td>FDA<\/td><td>2024<\/td><\/tr><tr><td><strong>Tecelra<\/strong><\/td><td>Afamitresgene-cel<\/td><td>TCR-T<\/td><td>MAGE-A4+HLA<\/td><td>Synovial sarcoma<\/td><td>FDA<\/td><td>2024<\/td><\/tr><tr><td><strong>Aucatzyl<\/strong><\/td><td>Obecabtagene-cel<\/td><td>CAR-T<\/td><td>CD19<\/td><td>Adult B-ALL<\/td><td>FDA<\/td><td>2024<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Nebenwirkungen_%E2%80%93_Was_alle_Therapien_verbindet\"><\/span>Side effects - what all therapies have in common<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>The most important common risks:<\/p>\n\n\n\n<p><strong>Cytokine storm (CRS)<\/strong><br>Occurs frequently with CAR-T and TCR-T; rarely with TIL.<br>Treatment with tocilizumab.<br>Since 2024 on all CAR-T labels: Boxed warning for secondary T-cell malignancies (very rare, ~3.6 % within years).<\/p>\n\n\n\n<p><strong>ICANS (Neurotoxicity)<\/strong><br>Immune cell-associated neurotoxicity syndrome; known in CAR-T, less common in TIL.<\/p>\n\n\n\n<p><strong>Cytopenias<\/strong><br>The necessary lymphodepletion (chemotherapy before infusion) always results in short-term blood count changes.<\/p>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Wo_werden_diese_Therapien_in_Deutschland_angeboten\"><\/span>Where are these therapies offered in Germany?<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>All FDA\/EMA-approved CAR-T products are manufactured in <strong>specialized transplant centers<\/strong> certified by the manufacturers and accredited by DKMS\/EBMT:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>University Medical Center Hamburg-Eppendorf (UKE):<\/strong> <a href=\"https:\/\/www.uke.de\" target=\"_blank\" rel=\"noopener\">uke.de<\/a><\/li>\n\n\n\n<li><strong>Charit\u00e9 - University Medicine Berlin:<\/strong> <a href=\"https:\/\/www.charite.de\" target=\"_blank\" rel=\"noopener\">charite.de<\/a><\/li>\n\n\n\n<li><strong>LMU Hospital Munich:<\/strong> <a href=\"https:\/\/www.lmu-klinikum.de\" target=\"_blank\" rel=\"noopener\">lmu-klinikum.de<\/a><\/li>\n\n\n\n<li><strong>Heidelberg University Hospital \/ KiTZ:<\/strong> <a href=\"https:\/\/www.kitz-heidelberg.de\" target=\"_blank\" rel=\"noopener\">kitz-heidelberg.de<\/a> <em>(also: PRAME research)<\/em><\/li>\n\n\n\n<li><strong>University Hospital Frankfurt:<\/strong> <a href=\"https:\/\/www.uniklinik-frankfurt.de\" target=\"_blank\" rel=\"noopener\">uniklinik-frankfurt.de<\/a><\/li>\n\n\n\n<li><strong>University Medical Center Freiburg:<\/strong> <a href=\"https:\/\/www.uniklinik-freiburg.de\" target=\"_blank\" rel=\"noopener\">uniklinik-freiburg.de<\/a><\/li>\n\n\n\n<li><strong>University Hospital D\u00fcsseldorf \/ Essen:<\/strong> specialized in MCL\/DLBCL-CAR-T<\/li>\n<\/ul>\n\n\n\n<p><strong>Complete list of certified CAR-T centers:<\/strong> <a href=\"https:\/\/www.ebmt.org\/registry\/center-search\" target=\"_blank\" rel=\"noopener\">EBMT Center Search<\/a><\/p>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ausblick_Was_kommt_als_nachstes\"><\/span>Outlook: What's next?<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>The next wave of approved immune cell therapies is expected to come in 2026-2028:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>IMA203 \/ Anzu-cel (PRAME-TCR):<\/strong> Phase 3 SUPRAME trial underway - <em>Possible approval for melanoma 2027\/2028<\/em><\/li>\n\n\n\n<li><strong>Lifileucel + pembrolizumab (Phase 3):<\/strong> First-line study NCT05727904 - <em>Possible first-line approval for melanoma<\/em><\/li>\n\n\n\n<li><strong>Brenetafusp (PRISM-MEL-301):<\/strong> Phase 3 study PRAME\u00d7CD3-Bispecific - <em>Possible approval 2027<\/em><\/li>\n\n\n\n<li><strong>CAR-T for autoimmune diseases (SLE, MS):<\/strong> Phase 2 trials underway; potentially first non-oncology CAR-T product<\/li>\n\n\n\n<li><strong>KiTZ Heidelberg pediatric PRAME study:<\/strong> planned for 2026 - first study for children worldwide<\/li>\n<\/ul>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h1 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"GKV-Erstattung_von_Immunzelltherapien_in_Deutschland\"><\/span>SHI reimbursement of immune cell therapies in Germany<span class=\"ez-toc-section-end\"><\/span><\/h1>\n\n\n\n<p>Status 02.2026<\/p>\n\n\n\n<p>The situation is complex and varies greatly depending on the type of therapy, product and health insurance provider. There is no blanket, automatic reimbursement as there is for traditional medicines. Instead, there is a multi-stage system with a considerable amount of bureaucracy, which doctors and clinics openly criticize as dysfunctional.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"CAR-T-Zelltherapien\"><\/span>CAR-T cell therapies<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>Generally refundable, but complicated<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"AMNOG_NUB-Verfahren\"><\/span>AMNOG &amp; NUB procedure<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>CAR-T preparations are <strong>Advanced therapy medicinal products (ATMP)<\/strong> and are subject to the German <strong>AMNOG procedure<\/strong> (Pharmaceutical Market Reorganization Act). This provides for<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Fruhe_Nutzenbewertung_durch_den_G-BA\"><\/span>Early benefit assessment by the G-BA<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>Since January 1, 2011, the G-BA has had the statutory task of conducting a benefit assessment for all newly approved medicinal products with new active substances immediately after market entry.<br>It is tested whether the new drug is superior to the previous standard therapy - the so-called <strong>appropriate comparator therapy<\/strong> - offers an advantage.<\/p>\n\n\n\n<p><strong>Legal basis:<\/strong> <a href=\"https:\/\/www.gesetze-im-internet.de\/sgb_5\/__35a.html\" target=\"_blank\" rel=\"noopener\">\u00a7 Section 35a SGB V - Evaluation of the benefit of medicinal products (legal wording)<\/a><\/p>\n\n\n\n<p><strong>Procedure description G-BA:<\/strong> <a href=\"https:\/\/www.g-ba.de\/themen\/arzneimittel\/arzneimittel-richtlinie-anlagen\/nutzenbewertung-35a\/\" target=\"_blank\" rel=\"noopener\">g-ba.de - AMNOG benefit assessment according to \u00a7 35a SGB V<\/a><\/p>\n\n\n\n<p>The result of this benefit assessment is the starting point for the price negotiations between the GKV-Spitzenverband and the pharmaceutical manufacturer.<br>The possible categories for the assessment of added benefit are defined in the German Drug Benefit Assessment Ordinance and in Chapter 5 of the G-BA's Code of Procedure.<\/p>\n\n\n\n<p>The four categories of additional benefit are:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Significant<\/strong> Additional benefits<\/li>\n\n\n\n<li><strong>Considerable<\/strong> Additional benefits<\/li>\n\n\n\n<li><strong>Lower<\/strong> Additional benefits<\/li>\n\n\n\n<li><strong>None<\/strong> Proven additional benefit<\/li>\n<\/ul>\n\n\n\n<p><strong>The four categories in the original wording:<\/strong> <a href=\"https:\/\/www.g-ba.de\/themen\/arzneimittel\/arzneimittel-richtlinie-anlagen\/nutzenbewertung-35a\/zusatznutzen\/\" target=\"_blank\" rel=\"noopener\">g-ba.de - Categories of added value<\/a><\/p>\n\n\n\n<p><strong>Legal basis of the categories:<\/strong> <a href=\"https:\/\/www.gesetze-im-internet.de\/am-nutzenv\/BJNR232400010.html\" target=\"_blank\" rel=\"noopener\">AM-NutzenV \u00a7 5 para. 7 - Drug Benefit Assessment Ordinance (legal wording)<\/a><\/p>\n\n\n\n<p><strong>Specific example: G-BA procedure for Yescarta (CAR-T):<\/strong> <a href=\"https:\/\/www.g-ba.de\/bewertungsverfahren\/nutzenbewertung\/406\/\" target=\"_blank\" rel=\"noopener\">g-ba.de - Benefit assessment procedure Axicabtagene-Ciloleucel<\/a><\/p>\n\n\n\n<p><strong>All ongoing and completed G-BA assessment procedures:<\/strong> <a href=\"https:\/\/www.g-ba.de\/bewertungsverfahren\/nutzenbewertung\/\" target=\"_blank\" rel=\"noopener\">g-ba.de - Evaluation procedure overview<\/a><\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Preisverhandlung_nach_%C2%A7_130b_SGB_V\"><\/span>Price negotiation according to \u00a7 130b SGB V<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>On the basis of the G-BA's decision on the additional benefit of the new drug, the GKV-Spitzenverband and the pharmaceutical company usually negotiate the so-called reimbursement amount in four negotiation meetings within six months. This applies from the seventh month after market launch as the new nationwide dispensing price - for those with statutory health insurance, private insurance and self-payers alike.<\/p>\n\n\n\n<p><strong>Legal basis:<\/strong> <a href=\"https:\/\/www.gesetze-im-internet.de\/sgb_5\/__130b.html\" target=\"_blank\" rel=\"noopener\">\u00a7 Section 130b SGB V - Agreements on reimbursement amounts (wording of the law)<\/a><\/p>\n\n\n\n<p><strong>Procedure description GKV-Spitzenverband:<\/strong> <a href=\"https:\/\/www.gkv-spitzenverband.de\/krankenversicherung\/arzneimittel\/verhandlungen_nach_amnog\/rabatt_verhandlungen_nach_amnog.jsp\" target=\"_blank\" rel=\"noopener\">gkv-spitzenverband.de - AMNOG negotiations according to \u00a7 130b SGB V<\/a><\/p>\n\n\n\n<p><strong>Overview of all negotiated reimbursement amounts (incl. CAR-T products):<\/strong> <a href=\"https:\/\/www.gkv-spitzenverband.de\/krankenversicherung\/arzneimittel\/verhandlungen_nach_amnog\/ebv_130b\/ebv_nach_130b.jsp\" target=\"_blank\" rel=\"noopener\">gkv-spitzenverband.de - Reimbursement amount agreements<\/a><\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"NUB-Verfahren_fur_Krankenhauser\"><\/span>NUB procedure for hospitals<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>As CAR-T therapies are administered on an inpatient basis, the clinics are also subject to the <strong>NUB procedure<\/strong> (New examination and treatment methods in accordance with Section 6 (2) KHEntgG).<\/p>\n\n\n\n<p>The NUB procedure closes the so-called \u201einnovation gap\u201c, the period of usually three years until a new therapy is fully incorporated into the G-DRG flat rate system.<br>During this period, hospitals can negotiate hospital-specific NUB fees with the health insurance funds, provided that the Institute for the Hospital Remuneration System (InEK) awards status 1 following a review.<\/p>\n\n\n\n<p>Hospitals must submit NUB applications to InEK by October 31 each year. InEK publishes the results of its review by the end of January of the following year.<\/p>\n\n\n\n<p>For ATMPs (advanced therapy medicinal products) - which include all CAR-T and TCR-T products - an extended application deadline of April 30 of each year applies, unless the application has already been submitted by October 31.<\/p>\n\n\n\n<p><strong>NUB procedure officially (InEK):<\/strong> <a href=\"https:\/\/www.g-drg.de\/neue-untersuchungs-und-behandlungsmethoden-nub\/drg\" target=\"_blank\" rel=\"noopener\">g-drg.de - NUB procedure for ATMPs<\/a><\/p>\n\n\n\n<p><strong>NUB procedure (GKV-Spitzenverband):<\/strong> <a href=\"https:\/\/www.gkv-spitzenverband.de\/krankenversicherung\/krankenhaeuser\/drg_system\/neue_untersuchungs_und_behandlungsmethoden_nub\/neue_untersuchungs_und_behandlungsmethoden_nub.jsp\" target=\"_blank\" rel=\"noopener\">gkv-spitzenverband.de - NUB in hospitals<\/a><\/p>\n\n\n\n<p><strong>Detailed process explanation with ATMP special regulation:<\/strong> <a href=\"https:\/\/reimbursement.institute\/nub-antrag\/\" target=\"_blank\" rel=\"noopener\">reimbursement.institute - NUB request procedure<\/a><\/p>\n\n\n\n<p><strong>AOK overview NUB 2025 (with current status figures):<\/strong> <a href=\"https:\/\/www.aok.de\/gp\/krankenhaus\/verguetung-drg\/nub\" target=\"_blank\" rel=\"noopener\">aok.de\/gp - NUB in somatics<\/a><\/p>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Die_Realitat_Einzelfallantrage_und_Burokratie\"><\/span>The reality: individual applications and bureaucracy<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Despite negotiated reimbursement amounts, the practice for clinics and patients is considerably more complicated than the formal regulations would suggest.<\/p>\n\n\n\n<p>Until now, the centers have generally had to submit an individual application for cost coverage by statutory health insurance.<br>There is no standardized, automatic cost coverage for people with statutory health insurance.<\/p>\n\n\n\n<p><strong>Source:<\/strong> <a href=\"https:\/\/www.krebsinformationsdienst.de\/fachkreise\/nachrichten\/detail\/update-car-t-zell-therapie\" target=\"_blank\" rel=\"noopener\">DKFZ Cancer Information Service - Update CAR-T: Individual application procedure and discount agreements<\/a><\/p>\n\n\n\n<p>As a CAR-T product costs several hundred thousand euros, clinics have to obtain cost coverage before they can start the therapy. Senior physician Dr. Veit B\u00fccklein from LMU Klinikum M\u00fcnchen describes the effort involved: \u201eWe have to fill out a checklist and collect many, many documents, from A for doctor's letter to Z for compilation of all findings.\u201c The official procedure is called the \u201eindividual cost reimbursement application procedure\u201c.<\/p>\n\n\n\n<p><strong>Source:<\/strong> <a href=\"https:\/\/pharma-fakten.de\/news\/car-t-zelltherapie-zukunftsversprechen-versus-burokratiemonster\/\" target=\"_blank\" rel=\"noopener\">Pharma facts - CAR-T: Promise of the future versus bureaucracy monster (LMU Klinikum M\u00fcnchen, September 2024)<\/a><\/p>\n\n\n\n<p>Prof. Dr. Marion Subklewe, head of the CAR-T program at LMU Klinikum M\u00fcnchen, sums up the criticism: \u201eWe work with approved products. I don't understand why I have to submit an individual application for an approved product every time.\u201c The reimbursement processes are currently \u201ean instrument to make progress more difficult\u201c.<\/p>\n\n\n\n<p><strong>Source:<\/strong> <a href=\"https:\/\/pharma-fakten.de\/news\/car-t-zelltherapien-optimale-versorgung-sieht-anders-aus\/\" target=\"_blank\" rel=\"noopener\">Pharma facts - CAR-T: Optimal care looks different (April 2025)<\/a><\/p>\n\n\n\n<p>Prof. Dr. Michael Hallek, Director of Clinic I for Internal Medicine at the University Hospital of Cologne, proposes the solution of systematically assigning CAR-T cell therapies to specialized centers that can document their work and demonstrate proven success, and then giving these centers a free hand in treatment decisions: \u201eThen you can forget about the review process, because who else but us is supposed to judge whether a treatment is right or not?\u201c<\/p>\n\n\n\n<p><strong>Source:<\/strong> <a href=\"https:\/\/pharma-fakten.de\/news\/car-t-zelltherapie-woran-es-noch-fehlt\/\" target=\"_blank\" rel=\"noopener\">Pharma facts - CAR-T: What is still missing (Event University Hospital Cologne, July 2025)<\/a><\/p>\n\n\n\n<p>From the university hospitals' point of view, the core structural problem is that the legislator has not closed the time gap between the approval of a drug and the hospitals' guaranteed entitlement to reimbursement. In the case of new cell and gene therapies, the financial risk for hospitals is too high for them to be able to make advance payments.<\/p>\n\n\n\n<p><strong>Source:<\/strong> <a href=\"https:\/\/www.uniklinika.de\/gesundheitspolitischethemen\/car-t-zelltherapie\/\" target=\"_blank\" rel=\"noopener\">Uniklinika.de - CAR-T cell therapy: demand for reimbursement security<\/a><\/p>\n\n\n\n<p>The medical consequences of these delays are measurable: a one-month wait for CAR-T cell therapy can increase relative mortality by 6.2 percent. Any delay in access to CAR-T can have a direct impact on the success of treatment.<\/p>\n\n\n\n<p><strong>Source:<\/strong> <a href=\"https:\/\/pharma-fakten.de\/news\/car-t-zelltherapien-optimale-versorgung-sieht-anders-aus\/\" target=\"_blank\" rel=\"noopener\">Pharma-Fakten \/ IQVIA Institute - CAR-T: Optimal care looks different (with reference to IQVIA study)<\/a><\/p>\n\n\n\n<p>In addition, there is another structural problem: over 160 hospitals have submitted NUB applications to be able to offer CAR-T therapies - but initially only received NUB status 4, which means that the SHI is not obliged to cover the costs as part of NUB agreements.<\/p>\n\n\n\n<p><strong>Source:<\/strong> <a href=\"https:\/\/www.vdek.com\/magazin\/ausgaben\/2018-1112\/politik_car_t_zelltherapie.html\" target=\"_blank\" rel=\"noopener\">VDEK - Revolution in oncology: NUB status and reimbursement issues for CAR-T<\/a><\/p>\n\n\n\n<p>Prof. Subklewe describes a particularly absurd individual example from everyday hospital life: \u201eI have to be told that a gastroenterologist has to be nearby 24 hours a day, even though I've never needed one in the last five years.\u201c<br>While certain quality and structural requirements make sense, they should not be allowed to get out of hand as they are at present.<\/p>\n\n\n\n<p><strong>Source:<\/strong> <a href=\"https:\/\/pharma-fakten.de\/news\/car-t-zelltherapie-zukunftsversprechen-versus-burokratiemonster\/\" target=\"_blank\" rel=\"noopener\">Pharma facts - CAR-T: Promise of the future versus bureaucracy monster<\/a><\/p>\n\n\n\n<p><strong>Overview of qualified CAR-T centers in Germany<\/strong> (for patients and referring physicians):<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/www.novartis.com\/de-de\/uebersicht-behandelnder-car-t-zentren-deutschland\" target=\"_blank\" rel=\"noopener\">Novartis - Overview of CAR-T treatment centers in Germany (Kymriah)<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/www.lmu-klinikum.de\/aktuelles\/pressemitteilungen\/funf-jahre-car-t-zelltherapie-am-lmu-klinikum-nbsp\/c52167393f8351f2\" target=\"_blank\" rel=\"noopener\">LMU Klinikum M\u00fcnchen - Five years of CAR-T: Program and contact<\/a> <\/li>\n\n\n\n<li><a href=\"https:\/\/www.dkfz.de\/de\/presse\/pressemitteilungen\/2020\/dkfz-pm-20-40-CAR-T-Zell-Therapien-erhebliche-Kostenersparnis-moeglich.php\" target=\"_blank\" rel=\"noopener\">DKFZ - CAR T-cell therapy: cost savings through in-house production<\/a><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Das_%E2%80%9EPay-for-Outcome%E2%80%9C-Modell\"><\/span>The \u201epay-for-outcome\u201c model<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p> (performance-related reimbursement)<\/p>\n\n\n\n<p>As an innovative interim solution, individual health insurance funds have developed so-called <strong>Pay-for-performance contracts<\/strong> closed:<\/p>\n\n\n\n<p>Novartis and GWQ ServicePlus have concluded a success-oriented reimbursement model for Kymriah, the first agreement of its kind in Germany:<br>Novartis will reimburse part of the drug costs if the patient dies of blood cancer within a defined period after treatment. <br>The outcome parameter is the survival of the treated patient.<\/p>\n\n\n\n<p>This model has set a precedent: Techniker Krankenkasse and other substitute health insurance funds have followed suit with similar agreements.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Welche_CAR-T-Produkte_sind_in_Deutschland_erstattungsfahig\"><\/span>Which CAR-T products are eligible for reimbursement in Germany?<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Product<\/th><th>Indication<\/th><th>SHI status<\/th><\/tr><\/thead><tbody><tr><td><strong>Kymriah<\/strong> (Tisagenlecleucel)<\/td><td>B-ALL pediatric, DLBCL, FL<\/td><td>\u2705 Refund amount negotiated (since Sept. 2019)<\/td><\/tr><tr><td><strong>Yescarta<\/strong> (Axicabtagene-cel)<\/td><td>DLBCL, PMBCL, FL, tFL<\/td><td>\u2705 Refund amount negotiated<\/td><\/tr><tr><td><strong>Tecartus<\/strong> (Brexucabtagene-cel)<\/td><td>MCL, adult B-ALL<\/td><td>\u2705 EMA-approved; NUB procedure ongoing\/completed<\/td><\/tr><tr><td><strong>Breyanzi<\/strong> (Lisocabtagene-cel)<\/td><td>DLBCL, CLL, FL<\/td><td>EMA-approved; NUB procedure<\/td><\/tr><tr><td><strong>Abecma<\/strong> (Idecabtagene-cel)<\/td><td>Multiple myeloma<\/td><td>EMA-approved; NUB procedure<\/td><\/tr><tr><td><strong>Carvykti<\/strong> (Ciltacabtagene-cel)<\/td><td>Multiple myeloma<\/td><td>EMA-approved; NUB procedure<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p><strong>Practical requirement in any case<\/strong><br>The treating center must<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>fulfill the ATMP quality assurance guideline of the G-BA<\/li>\n\n\n\n<li>FACT\/JACIE accredited<\/li>\n\n\n\n<li>and be certified as a CAR-T center.<\/li>\n<\/ul>\n\n\n\n<p>Only then can NUB fees be agreed and billed.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Kimmtrak_Tebentafusp_%E2%80%93_Sonderfall\"><\/span>Kimmtrak (Tebentafusp) - special case<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>Kimmtrak is not a cell product, but a <strong>Biopharmaceutical<\/strong> and is subject to the regular AMNOG procedure like other cancer drugs. It is administered on an outpatient basis and is generally reimbursable via the usual oncology billing pathways, but only for the approved indication (<strong>HLA-A*02:01-positive uveal melanoma<\/strong>, first line).<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"TIL-Therapie_Lifileucel_Amtagvi_%E2%80%93_In_Deutschland_derzeit_NICHT_erstattungsfahig\"><\/span>TIL therapy (Lifileucel \/ Amtagvi) - Currently NOT reimbursable in Germany<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>This is the most important current difference compared to the USA.<\/p>\n\n\n\n<p>The company <em>Iovance<\/em> withdrew its application for approval from the EMA on July 22, 2025. <\/p>\n\n\n\n<p>The EMA had concerns about the response rate in the main study as well as serious safety concerns, in some cases the therapy was associated with deaths.<br>In addition, the manufacturer lacked sufficient GMP documentation. <a href=\"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2025.43.16_suppl.TPS2673\" target=\"_blank\" rel=\"noreferrer noopener\">American Society of Clinical Oncology<\/a><\/p>\n\n\n\n<p>Iovance is currently developing a new strategy together with the EMA to obtain EU approval for Amtagvi. For the UK, approval is expected in the first half of 2026; Australia has granted Priority Review. <a href=\"https:\/\/www.globenewswire.com\/de\/news-release\/2025\/03\/27\/3050384\/0\/en\/Immatics-Announces-Full-Year-2024-Financial-Results-and-Business-Update.html\" target=\"_blank\" rel=\"noreferrer noopener\">GlobeNewswire<\/a><\/p>\n\n\n\n<p><strong>Conclusion for Germany:<\/strong> Lifileucel is currently available in the EU <strong>Not approved and not reimbursable<\/strong>. Patients who want this therapy must currently receive it in the USA, at their own expense or as part of clinical trials.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"TCR-T-Therapien_Afami-cel_Tecelra_%E2%80%93_In_Europa_nicht_zugelassen\"><\/span>TCR-T therapies (Afami-cel \/ Tecelra) - Not approved in Europe<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>Afamitresgene autoleucel (Tecelra) is currently <strong>only approved in the USA<\/strong> (FDA, August 2024). An EMA application has not yet been submitted.<\/p>\n\n\n\n<p>The following therefore applies to Germany: no reimbursement, no regular access, only via clinical studies or individual treatment trials (as in the case of Mailo at the KiTZ Heidelberg).<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Was_tun_wenn_die_Kasse_ablehnt_Rechtliche_Moglichkeiten\"><\/span>What to do if the health insurance company refuses? Legal options<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>If a statutory health insurer refuses to cover the costs of an EMA-approved therapy, the following options are available:<\/p>\n\n\n\n<p><strong>Objection (\u00a7 78 SGB V)<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Submit an objection in writing within 4 weeks of rejection.<\/li>\n\n\n\n<li>The clinic and doctor should enclose a detailed medical report.<\/li>\n<\/ul>\n\n\n\n<p><strong>Social court action<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>If the decision is still negative, file a complaint with the competent social court.<\/li>\n\n\n\n<li>In the case of life-threatening illnesses, a <strong>interim legal protection<\/strong> can be applied for, <br>the court can provisionally order the assumption of costs.<\/li>\n<\/ul>\n\n\n\n<p><strong>\u00a7 Section 2 (1a) SGB V (Nikolaus resolution)<\/strong><\/p>\n\n\n\n<p>In the case of life-threatening illnesses and a lack of standard therapy, insured persons are entitled to a non-standard approved therapy if there is a serious prospect of a cure or noticeable relief. This is the central legal instrument for cases such as individual treatment attempts.<\/p>\n\n\n\n<p><strong>Important resources:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/www.g-ba.de\/themen\/arzneimittel\/arzneimittel-richtlinie-anlagen\/nutzenbewertung-131e\/\" target=\"_blank\" rel=\"noopener\">G-BA benefit assessments of immune cell therapies<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/www.dgho.de\/arbeitskreise\/a-g\/drg-gesundheitsoekonomie\/nub-2025\/nub-2025\" target=\"_blank\" rel=\"noopener\">DGHO NUB templates 2025<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/www.krebsinformationsdienst.de\/fachkreise\/nachrichten\/detail\/update-car-t-zell-therapie\" target=\"_blank\" rel=\"noopener\">DKFZ Cancer Information Service - CAR-T and GKV<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/pharma-fakten.de\/news\/car-t-zelltherapie-woran-es-noch-fehlt\/\" target=\"_blank\" rel=\"noopener\">Pharma facts: Bureaucracy problem CAR-T<\/a><\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Osterreich\"><\/span>Austria<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p><strong>Austria:<\/strong> CAR-T cell therapy was included in the LKF service catalog in Austria on January 1, 2020 (group MEL22.30: \u201eAdministration of modified cells\u201c) - thus regulated earlier and more clearly than in Germany. <a href=\"https:\/\/www.clinicaltrialvanguard.com\/news\/t-knife-files-for-phase-1-trial-of-prame-t-cell-therapy\/\" target=\"_blank\" rel=\"noreferrer noopener\">Clinicaltrialvanguard<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Schweiz\"><\/span>Switzerland<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p><strong>Switzerland:<\/strong> Reimbursement via the KVG (Health Insurance Act) after inclusion in the FOPH's list of specialties; for EMA-approved CAR-T products possible in principle, also with individual case assessment.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zusammenfassung\"><\/span>Summary<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Therapy<\/th><th>EU approval<\/th><th>SHI reimbursement Germany<\/th><\/tr><\/thead><tbody><tr><td>CAR-T (Kymriah, Yescarta, Tecartus, Breyanzi, Abecma, Carvykti)<\/td><td>Yes (EMA)<\/td><td>Basically yes - but via individual case application\/NUB, with considerable bureaucracy<\/td><\/tr><tr><td>Kimmtrak (Tebentafusp)<\/td><td>Yes (EMA)<\/td><td>Yes (AMNOG procedure, outpatient)<\/td><\/tr><tr><td>Lifileucel \/ Amtagvi (TIL)<\/td><td>No (EMA application withdrawn July 2025)<\/td><td>No<\/td><\/tr><tr><td>Afami-cel \/ Tecelra (TCR-T)<\/td><td>No (FDA only)<\/td><td>No<\/td><\/tr><tr><td>PRAME-TCR (IMA203, experimental)<\/td><td>No (Phase 3)<\/td><td>No - only via study participation<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p>The central political problem remains: To date, there is no really good legal and financing framework for quickly and reliably reflecting these innovative therapies in the German system. It can take years before a medical innovation is correctly reflected in the flat rate per case system.<\/p>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"PKV_und_Immunzelltherapie_%E2%80%93_Die_vollstandige_Rechtslage\"><\/span>PKV and immune cell therapy - The complete legal situation<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>Status: February 2026<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Das_rechtliche_Fundament_%C2%A7_192_VVG_und_MBKK_2009\"><\/span>The legal foundation: \u00a7 192 VVG and MB\/KK 2009<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>In the case of medical expenses insurance, the insurer is obliged to reimburse the expenses for medically necessary treatment due to illness or the consequences of an accident to the extent agreed. The insurer is not obliged to pay benefits if the expenses for medical treatment or other benefits are conspicuously disproportionate to the benefits provided.<\/p>\n\n\n\n<p><strong>Legal wording \u00a7 192 VVG (complete):<\/strong> <a href=\"https:\/\/dejure.org\/gesetze\/VVG\/192.html\" target=\"_blank\" rel=\"noopener\">dejure.org - Section 192 VVG Typical contractual benefits of the insurer<\/a><\/p>\n\n\n\n<p><strong>Official sample conditions MB\/KK 2009 (PDF, PKV-Verband):<\/strong> <a href=\"https:\/\/www.pkv.de\/fileadmin\/user_upload\/PKV\/3_PDFs\/ABV_und_MB\/MB-KK.pdf\" target=\"_blank\" rel=\"noopener\">pkv.de - MB\/KK 2009 sample conditions<\/a><\/p>\n\n\n\n<p>The benefit obligations of private health insurers are essentially determined by the tariff selected in the individual case and the associated tariff conditions. According to \u00a7 192 Para. 1 VVG in conjunction with the MB\/KK, expenses for medically necessary treatment due to illness or the consequences of an accident are reimbursed.<\/p>\n\n\n\n<p><strong>Explanation of the PKV benefit obligation according to \u00a7 192 VVG:<\/strong> <a href=\"https:\/\/www.legal-plus.eu\/die-leistungspflicht-der-privaten-krankenversicherung-pkv-wann-und-wofuer-muss-die-pkv-zahlen\/\" target=\"_blank\" rel=\"noopener\">legal-plus.eu - The PKV's obligation to pay: When and for what does the PKV have to pay?<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Der_Schlusselbegriff_%E2%80%9EMedizinisch_notwendige_Heilbehandlung%E2%80%9C\"><\/span>The key term: \u201eMedically necessary treatment\u201c<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>According to established case law and in accordance with the model conditions MB\/KK and \u00a7 192 VVG, medical necessity exists if the treatment is suitable, according to objective medical findings and knowledge, to recognize an illness, cure it, prevent its worsening or alleviate symptoms. The decisive factor is whether, in the opinion of a competent doctor at the time of treatment, the measure appears necessary according to recognized scientific standards.<\/p>\n\n\n\n<p><strong>Legal analysis: Definition of medical necessity in private health insurance:<\/strong> <a href=\"https:\/\/kanzlei-neue-kraeme.de\/erstattung-kostenintensiver-behandlungsmassnahmen-in-der-pkv\/\" target=\"_blank\" rel=\"noopener\">kanzlei-neue-kraeme.de - Reimbursement of cost-intensive treatment measures under private health insurance<\/a><\/p>\n\n\n\n<p>In addition to treatments recognized by conventional medicine, private health insurance also reimburses treatments that have proven equally promising in practice or for which there is no alternative. These can also be new drugs or innovative diagnostic procedures and treatment methods that are considered useful by experts.<\/p>\n\n\n\n<p><strong>PKV Association: Official explanation of benefits and reimbursement (incl. innovative therapies):<\/strong> <a href=\"https:\/\/www.pkv.de\/wissen\/private-krankenversicherung\/leistungen-und-erstattung\/\" target=\"_blank\" rel=\"noopener\">pkv.de - Benefits and reimbursement in private health insurance<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Das_Richtungsurteil_OLG_Frankfurt_29062022_%E2%80%93_Az_7_U_14021\"><\/span>The landmark judgment: OLG Frankfurt, 29.06.2022 - Ref. 7 U 140\/21<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>This is the central ruling for the reimbursement of immune cell therapies by private health insurers in Germany.<\/p>\n\n\n\n<p><strong>Facts of the case<\/strong><br>A patient had been diagnosed with a non-operable pancreatic tumor. After chemotherapy failed, he decided against standard palliative therapy, which offered a lower prognosis of success, and instead opted for dendritic cell therapy. He wanted to claim the costs from his private health insurance company, but it refused to pay in full.<\/p>\n\n\n\n<p><strong>Verdict<\/strong><br>Dendritic cell therapy is a medical treatment within the meaning of the medical cost conditions (MB\/KK 2009) of private health insurance companies. If a conventional first-line therapy does not lead to the desired treatment success for a person suffering from a life-destroying and incurable tumor, the insured person does not have to be referred to a second-line therapy with an even lower prognosis of effectiveness. Rather, they can demand direct payment of the costs of a new, scientifically sound alternative therapy if, at the time of treatment, this offers a not entirely remote prospect of achieving success beyond that of standard palliative therapy.<\/p>\n\n\n\n<p><strong>Full discussion of the judgment (DATEV Magazin):<\/strong> <a href=\"https:\/\/www.datev-magazin.de\/nachrichten-steuern-recht\/recht\/private-krankenversicherung-muss-bei-inoperablem-tumor-nach-gescheiterter-chemotherapie-kosten-einer-alternativtherapie-mit-dendritischen-zellen-tragen-81762\" target=\"_blank\" rel=\"noopener\">datev-magazin.de - OLG Frankfurt: PKV must bear costs of dendritic cell therapy<\/a><\/p>\n\n\n\n<p><strong>Judgment review with confirmation of legal force (January 2023):<\/strong> <a href=\"https:\/\/transkript.de\/artikel\/2023\/krankenkasse-muss-zelltherapie-zahlen\/\" target=\"_blank\" rel=\"noopener\">transkript.de - Health insurance company must pay for cell therapy (incl. confirmation of legal force)<\/a><\/p>\n\n\n\n<p><strong>Judgment analysis for hospitals (IWW Verg\u00fctungsrecht):<\/strong> <a href=\"https:\/\/www.iww.de\/cb\/recht\/verguetungsrecht-schulmedizinische-behandlung-erfolglos-pkvmuss-kosten-der-alternativtherapie-tragen-f149155\" target=\"_blank\" rel=\"noopener\">iww.de - PKV must bear the costs of alternative therapy<\/a><\/p>\n\n\n\n<p><strong>Haufe: Brief summary of the judgment:<\/strong> <a href=\"https:\/\/www.haufe.de\/recht\/weitere-rechtsgebiete\/inoperabler-tumor-uebernahme-von-alternativtherapie-durch-pkv_216_571650.html\" target=\"_blank\" rel=\"noopener\">haufe.de - Inoperable tumor: Alternative therapy covered by PKV<\/a><\/p>\n\n\n\n<p><strong>Detailed analysis of the judgment (J\u00f6hnke &amp; Reichow Rechtsanw\u00e4lte):<\/strong> <a href=\"https:\/\/joehnke-reichow.de\/2024\/07\/17\/kostenerstattung-bei-einer-dendritischen-zellbehandlung-olg-frankfurt\/\" target=\"_blank\" rel=\"noopener\">joehnke-reichow.de - Reimbursement of costs for dendritic cell treatment, OLG Frankfurt<\/a><\/p>\n\n\n\n<p><strong>Legal force:<\/strong> According to the Hessian Higher Regional Court, the deadline for filing an appeal has expired, meaning that the decision has been legally binding since January 2023.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Das_%E2%80%9Eauffallige_Missverhaltnis%E2%80%9C_nach_%C2%A7_192_Abs_2_VVG_%E2%80%93_und_warum_es_bei_CAR-T_nicht_greift\"><\/span>The \u201econspicuous disproportion\u201c pursuant to Section 192 (2) VVG - and why it does not apply to CAR-T<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>The burden of presentation and proof for the existence of a conspicuous disproportion lies with the insurer. There is agreement that the usual value of the service provided is decisive and not the price for the medical minimum. Applying the case law of the Federal Court of Justice on usury offenses, a market comparison is a suitable means of determining the objective value.<\/p>\n\n\n\n<p>Since CAR-T therapies are priced at a comparable level worldwide (\u20ac 250,000-600,000), a \u201econspicuous imbalance\u201c can be invalidated by an international market comparison.<\/p>\n\n\n\n<p><strong>Legal analysis of the \u201econspicuous disproportion\u201c according to \u00a7 192 para. 2 VVG:<\/strong> <a href=\"https:\/\/www.kunzrechtsanwaelte.de\/aktuelles\/urteile\/versicherung-und-haftung\/krankenversicherung\" target=\"_blank\" rel=\"noopener\">kunzrechtsanwaelte.de - On the conspicuous disproportion within the meaning of Section 192 (2) VVG<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Das_Voranfrageverfahren_nach_%C2%A7_192_Abs_8_VVG_%E2%80%93_der_wichtigste_praktische_Schritt\"><\/span>The preliminary enquiry procedure in accordance with Section 192 (8) VVG - the most important practical step<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>As soon as it is foreseeable that the expected treatment costs will exceed \u20ac2,000, insured persons are entitled to information about the cost approval in accordance with Section 192 (8) VVG. The insurance company must confirm or reject the assumption of costs within 4 weeks of submission of the cost estimate.<\/p>\n\n\n\n<p>If the information is not provided within the deadline, it is assumed by the insurer that the intended medical treatment is necessary until the contrary is proven. This <strong>Fiction of necessity<\/strong> for failure to respond is an important protective instrument for patients.<\/p>\n\n\n\n<p><strong>Wording of the law \u00a7 192 para. 8 VVG (obligation to make an inquiry in advance):<\/strong> <a href=\"https:\/\/dejure.org\/gesetze\/VVG\/192.html\" target=\"_blank\" rel=\"noopener\">dejure.org - Section 192 (8) VVG<\/a><\/p>\n\n\n\n<p><strong>Practical instructions: Preliminary inquiry with the PKV before cost-intensive treatment:<\/strong> <a href=\"https:\/\/www.pkv-inhalte.de\/pkv-bu-av-blog\/pkv-versichert-und-teure-behandlung-steht-bevor-wie-geht-man-richtig-vor\/\" target=\"_blank\" rel=\"noopener\">pkv-inhalte.de - PKV insurance and expensive treatment: What's the right approach?<\/a><\/p>\n\n\n\n<p><strong>Legal consequences of incorrect or missing PKV information:<\/strong> <a href=\"https:\/\/www.versicherungsrechtsiegen.de\/krankenhauskosten-zusatzversicherung-kostenerstattung-fuer-aufenthalt-in-privatklinik\/\" target=\"_blank\" rel=\"noopener\">versicherungsrechtsiegen.de - Cost commitment and \u00a7 192 para. 8 VVG in practice<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Bei_Ablehnung_Rechtsmittel_und_Klage\"><\/span>In case of rejection: appeal and legal action<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>The question of reimbursement is determined by the interaction of \u00a7 192 VVG, the model conditions MB\/KK and the individual tariff clauses. The decisive factor is whether treatment was carried out due to illness and whether it was medically necessary.<\/p>\n\n\n\n<p>In the event of rejection by the PKV, the following options are available:<\/p>\n\n\n\n<p><strong>Objection with complete medical dossier<\/strong> (medical opinion, tumor board protocol, international study situation, cost estimate)<\/p>\n\n\n\n<p><strong>Action before the civil court<\/strong> (not social court, that is the difference to statutory health insurance) with application for interim injunction in case of urgent need for treatment<\/p>\n\n\n\n<p><strong>Complete guide: Contesting a PKV refusal, objection and legal action:<\/strong> <a href=\"https:\/\/kanzlei-neue-kraeme.de\/erstattung-kostenintensiver-behandlungsmassnahmen-in-der-pkv\/\" target=\"_blank\" rel=\"noopener\">kanzlei-neue-kraeme.de - Reimbursement of cost-intensive treatments under private health insurance<\/a><\/p>\n\n\n\n<p><strong>Refusal of private health insurance and benefits: legal steps at a glance:<\/strong> <a href=\"https:\/\/kva-plus.de\/ablehnung-der-kostenuebernahme-durch-die-pkv-und-beihilfe\/\" target=\"_blank\" rel=\"noopener\">kva-plus.de - Rejection of cost coverage by private health insurance and state aid<\/a><\/p>","protected":false},"excerpt":{"rendered":"<p><span class=\"span-reading-time rt-reading-time\" style=\"display: block;\"><span class=\"rt-label rt-prefix\">Reading time<\/span> <span class=\"rt-time\"> 20<\/span> <span class=\"rt-label rt-postfix\">minutes<\/span><\/span>Das Immunsystem &#8211; was macht das? Das Immunsystem unterh\u00e4lt eine ganze Armee von Kundschaftern, K\u00e4mpfern (T-Zellen) und Helfern. Sie patrouillieren st\u00e4ndig durch den K\u00f6rper und suchen nach Eindringlingen, wie Bakterien, Viren, aber auch wild gewordene k\u00f6rpereigene Zellen &#8211; Krebszellen. Normalerweise werden solch randalierende Zellen von den W\u00e4chtern des immunsystems schnell entdeckt, abget\u00f6tet, deren \u00dcberreste abtransportiert&hellip;&nbsp;<a href=\"https:\/\/csiag.de\/en\/blog\/2026\/02\/19\/immunzelltherapie\/\" rel=\"bookmark\">Read More \"<span class=\"screen-reader-text\">Immune cell therapy<\/span><\/a><\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_lmt_disableupdate":"","_lmt_disable":"","neve_meta_sidebar":"","neve_meta_container":"","neve_meta_enable_content_width":"","neve_meta_content_width":0,"neve_meta_title_alignment":"","neve_meta_author_avatar":"","neve_post_elements_order":"","neve_meta_disable_header":"","neve_meta_disable_footer":"","neve_meta_disable_title":"","footnotes":""},"categories":[5584,1078,354],"tags":[],"class_list":["post-12789","post","type-post","status-publish","format-standard","hentry","category-krebs","category-medizin","category-medizin-gesundheit"],"acf":[],"modified_by":"Achim Goerner","_links":{"self":[{"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/posts\/12789","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/comments?post=12789"}],"version-history":[{"count":0,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/posts\/12789\/revisions"}],"wp:attachment":[{"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/media?parent=12789"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/categories?post=12789"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/tags?post=12789"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}