{"entity":{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","aka":["CAR-T","CAR T cells","CAR T-cell therapy","Chimeric antigen receptor T cells"],"tldr":"A patient's T cells are removed, given a synthetic receptor that recognises the cancer, multiplied, and put back as a living drug.","summary":"Seven approved autologous products: CD19 (tisagenlecleucel, axicabtagene, lisocabtagene, brexucabtagene, obecabtagene) and BCMA (idecabtagene, ciltacabtagene). Curative in a substantial fraction of relapsed large B-cell lymphoma and ALL; moving to second line and earlier in myeloma (CARTITUDE-4). Solid tumours: CLDN18.2 (satri-cel), GPC3, GD2 (neuroblastoma, glioma), B7-H3, IL13Rα2, and regionally delivered CARs. FDA removed REMS requirements in 2025; secondary T-cell malignancy warning added in 2024.\n\nThe design is Israeli in origin: Gross, Waks and Eshhar at the Weizmann Institute of Science built the first chimeric receptor in 1989, splicing antibody variable domains onto T-cell receptor constant domains so that a T cell killed its target without the major histocompatibility complex presenting it. They called it a T-body; costimulatory domains, the scFv format and the manufacturing came later.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell"},{"label":"Gross, Waks and Eshhar, the first chimeric antigen receptor (PNAS 1989)","url":"https://doi.org/10.1073/pnas.86.24.10024"},{"label":"Sotillo et al., Cancer Discov 2015: acquired mutations and alternative splicing of CD19 enable resistance to CART-19","url":"https://doi.org/10.1158/2159-8290.CD-15-1020"},{"label":"Deng et al., Nat Med 2020: single-cell features of the axicabtagene ciloleucel infusion product that track efficacy and toxicity in 24 patients","url":"https://doi.org/10.1038/s41591-020-1061-7"}],"tags":[],"related":[],"cancers":["dlbcl","follicular-lymphoma","mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["cell-therapy"],"technologies":["in-vivo-car-t","allogeneic-cell-therapy","armored-car"],"targets":["cd19","bcma","cldn18-2","gpc3","gprc5d","cd70","mesothelin"],"drugs":["ciltacabtagene-autoleucel","axicabtagene-ciloleucel","satricabtagene-autoleucel"],"companies":["cellogen","adicet-bio","allotera-therapeutics","arcellx","cargo-therapeutics","century-therapeutics","imugene","leah-labs","lyell-immunopharma","modulari-t","poseida-therapeutics","tmunity-therapeutics","cartesian-therapeutics","vor-biopharma","cartx-therapeutics","juventas-cell-therapy"],"institutions":[],"pathways":[],"terms":["crs","icans","lymphoma-bio-antigen-escape","lymphoma-bio-lineage-antigen-cost"],"trials":["nct07036250","nct05759728","nct07103668"],"people":["zelig-eshhar"],"bottlenecks":[],"keyPapers":["paper-gross-eshhar-chimeric-receptor-pnas-1989"],"journals":[],"dependsOn":["apheresis-starting-material","viral-vector-manufacturing","cell-therapy-cold-chain","cell-therapy-release-testing","cell-therapy-orchestration-software"],"notes":["Lymphoma: failure comes in two shapes and they need different answers. Relapse without the antigen, through deletion, exon 2 mutation or selection for a spliced transcript the receptor cannot see (Sotillo 2015), is answered by changing the address. Relapse with the antigen still there is usually about the cells: single-cell sequencing of 24 axicabtagene ciloleucel products found three times the frequency of memory-signature CD8 T cells in patients who reached complete response at three months, and an exhaustion signature that tracked a poor molecular response at day 7 (Deng 2020). Collecting T cells earlier in the disease course, allogeneic and in vivo products, and armoured constructs are the responses to the second."],"principle":"T cells are transduced with a lentiviral or retroviral chimeric antigen receptor (scFv + costimulatory domain + CD3ζ), infused after lymphodepletion, and expand in vivo.","strengths":["Single infusion, durable remissions","MHC-independent recognition"],"limitations":["Manufacturing time and cost (~$400k+)","CRS, ICANS, cytopenias","Solid-tumour antigen heterogeneity, trafficking, exhaustion"],"since":2017},"route":"/technologies/car-t/","neighbours":{"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"hcc-advanced","kind":"cancer","name":"Advanced hepatocellular carcinoma (BCLC C)","route":"/cancers/hcc-advanced/"},{"id":"burkitt-lymphoma","kind":"cancer","name":"Burkitt lymphoma","route":"/cancers/burkitt-lymphoma/"},{"id":"childhood-cancers","kind":"cancer","name":"Childhood cancers (all types)","route":"/cancers/childhood-cancers/"},{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"dipg-dmg","kind":"cancer","name":"Diffuse midline glioma, H3 K27-altered (including DIPG)","route":"/cancers/dipg-dmg/"},{"id":"ewing-sarcoma","kind":"cancer","name":"Ewing sarcoma","route":"/cancers/ewing-sarcoma/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"neuroblastoma-high-risk","kind":"cancer","name":"High-risk neuroblastoma","route":"/cancers/neuroblastoma-high-risk/"},{"id":"hiv-associated-lymphoma","kind":"cancer","name":"HIV-associated (AIDS-related) lymphomas","route":"/cancers/hiv-associated-lymphoma/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"neuroblastoma","kind":"cancer","name":"Neuroblastoma (paediatric)","route":"/cancers/neuroblastoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"osteosarcoma","kind":"cancer","name":"Osteosarcoma","route":"/cancers/osteosarcoma/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"post-transplant-lymphoproliferative-disorder","kind":"cancer","name":"Post-transplant lymphoproliferative disorder (PTLD)","route":"/cancers/post-transplant-lymphoproliferative-disorder/"},{"id":"primary-cns-lymphoma","kind":"cancer","name":"Primary CNS lymphoma","route":"/cancers/primary-cns-lymphoma/"},{"id":"primary-mediastinal-b-cell-lymphoma","kind":"cancer","name":"Primary mediastinal (thymic) large B-cell lymphoma","route":"/cancers/primary-mediastinal-b-cell-lymphoma/"},{"id":"all-paediatric-relapsed","kind":"cancer","name":"Relapsed and refractory acute lymphoblastic leukaemia in children","route":"/cancers/all-paediatric-relapsed/"},{"id":"relapsed-refractory-hodgkin-lymphoma","kind":"cancer","name":"Relapsed and refractory classical Hodgkin lymphoma","route":"/cancers/relapsed-refractory-hodgkin-lymphoma/"},{"id":"cll-relapsed","kind":"cancer","name":"Relapsed or refractory chronic lymphocytic leukaemia","route":"/cancers/cll-relapsed/"},{"id":"myeloma-relapsed-refractory","kind":"cancer","name":"Relapsed or refractory multiple myeloma","route":"/cancers/myeloma-relapsed-refractory/"},{"id":"rhabdomyosarcoma","kind":"cancer","name":"Rhabdomyosarcoma","route":"/cancers/rhabdomyosarcoma/"},{"id":"richter-transformation-cll","kind":"cancer","name":"Richter transformation of chronic lymphocytic leukaemia","route":"/cancers/richter-transformation-cll/"}],"section":[{"id":"cell-therapy","kind":"section","name":"Cell Therapy","route":"/fronts/cell-therapy/"}],"technology":[{"id":"rejuv-tx-what-to-ask-for","kind":"technology","name":"After a transplant or cell therapy: what to ask for","route":"/technologies/rejuv-tx-what-to-ask-for/"},{"id":"allogeneic-cell-therapy","kind":"technology","name":"Allogeneic (off-the-shelf) cell therapy","route":"/technologies/allogeneic-cell-therapy/"},{"id":"allogeneic-cell-banks","kind":"technology","name":"Allogeneic cell banks: one donor, hundreds of doses","route":"/technologies/allogeneic-cell-banks/"},{"id":"allogeneic-cell-banking","kind":"technology","name":"Allogeneic donor and iPSC master cell banks","route":"/technologies/allogeneic-cell-banking/"},{"id":"apheresis-starting-material","kind":"technology","name":"Apheresis and starting-material collection","route":"/technologies/apheresis-starting-material/"},{"id":"armored-car","kind":"technology","name":"Armoured, logic-gated & next-gen CARs","route":"/technologies/armored-car/"},{"id":"car-t-manufacturing-process","kind":"technology","name":"Autologous CAR-T manufacturing, batch by batch","route":"/technologies/car-t-manufacturing-process/"},{"id":"rejuv-tx-b-cell-aplasia-and-immunoglobulin","kind":"technology","name":"B-cell aplasia and low antibodies after CAR-T and bispecifics, and immunoglobulin replacement","route":"/technologies/rejuv-tx-b-cell-aplasia-and-immunoglobulin/"},{"id":"rejuv-tx-prolonged-cytopenias","kind":"technology","name":"Blood counts that do not come back after CAR-T: ICAHT","route":"/technologies/rejuv-tx-prolonged-cytopenias/"},{"id":"car-nk-macrophage","kind":"technology","name":"CAR-NK & CAR-macrophage","route":"/technologies/car-nk-macrophage/"},{"id":"stroma-directed-car","kind":"technology","name":"CAR-T against stroma: fibroblasts and myeloid cells","route":"/technologies/stroma-directed-car/"},{"id":"glioma-car-t","kind":"technology","name":"CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)","route":"/technologies/glioma-car-t/"},{"id":"cell-therapy-orchestration-software","kind":"technology","name":"Cell-therapy orchestration and chain-of-identity software","route":"/technologies/cell-therapy-orchestration-software/"},{"id":"cell-therapy-release-testing","kind":"technology","name":"Cell-therapy release and potency testing","route":"/technologies/cell-therapy-release-testing/"},{"id":"closed-automated-cell-manufacturing","kind":"technology","name":"Closed automated cell-therapy manufacturing","route":"/technologies/closed-automated-cell-manufacturing/"},{"id":"cell-therapy-cold-chain","kind":"technology","name":"Cryopreservation and cell-therapy cold chain","route":"/technologies/cell-therapy-cold-chain/"},{"id":"gamma-delta-t-cell-therapy","kind":"technology","name":"Gamma-delta T cell therapy","route":"/technologies/gamma-delta-t-cell-therapy/"},{"id":"humanised-mouse-models","kind":"technology","name":"Humanised mouse models","route":"/technologies/humanised-mouse-models/"},{"id":"rejuv-tx-icans-and-neurocognition","kind":"technology","name":"ICANS, and whether thinking recovers after CAR-T","route":"/technologies/rejuv-tx-icans-and-neurocognition/"},{"id":"in-vivo-car-t","kind":"technology","name":"In vivo CAR-T","route":"/technologies/in-vivo-car-t/"},{"id":"rejuv-tx-infection-by-phase","kind":"technology","name":"Infection risk after transplant and cell therapy, phase by phase, and the prophylaxis that follows it","route":"/technologies/rejuv-tx-infection-by-phase/"},{"id":"logic-gated-therapeutics","kind":"technology","name":"Logic-gated therapeutics (AND, NOT gates)","route":"/technologies/logic-gated-therapeutics/"},{"id":"rejuv-tx-gene-modified-follow-up","kind":"technology","name":"Long-term follow-up for gene-modified cell products: fifteen years, and why","route":"/technologies/rejuv-tx-gene-modified-follow-up/"},{"id":"nk-cell-therapy","kind":"technology","name":"NK cell therapy and CAR-NK","route":"/technologies/nk-cell-therapy/"},{"id":"point-of-care-cell-manufacturing","kind":"technology","name":"Point-of-care and decentralised cell manufacturing","route":"/technologies/point-of-care-cell-manufacturing/"},{"id":"rejuv-tx-quality-of-life","kind":"technology","name":"Quality of life after transplant and cell therapy","route":"/technologies/rejuv-tx-quality-of-life/"},{"id":"rejuv-tx-immune-reconstitution-timeline","kind":"technology","name":"Rebuilding an immune system: the timeline, lineage by lineage","route":"/technologies/rejuv-tx-immune-reconstitution-timeline/"},{"id":"rejuv-frontier-immune-reconstitution","kind":"technology","name":"Rebuilding the immune system after treatment","route":"/technologies/rejuv-frontier-immune-reconstitution/"},{"id":"rejuv-tx-revaccination","kind":"technology","name":"Revaccination after transplant: the schedules, and where the UK and the US differ","route":"/technologies/rejuv-tx-revaccination/"},{"id":"rejuv-tx-secondary-t-cell-malignancy","kind":"technology","name":"Secondary T-cell malignancy after CAR-T, and what the FDA's 2024 action actually says","route":"/technologies/rejuv-tx-secondary-t-cell-malignancy/"},{"id":"immune-tumour-dynamics-models","kind":"technology","name":"Tumour-immune dynamics models","route":"/technologies/immune-tumour-dynamics-models/"},{"id":"viral-vector-manufacturing","kind":"technology","name":"Viral vector manufacturing (lentiviral, retroviral, AAV)","route":"/technologies/viral-vector-manufacturing/"},{"id":"rejuv-tx-long-term-follow-up-frameworks","kind":"technology","name":"Who is supposed to be watching: EBMT, CIBMTR, FACT-JACIE, and what a survivor is actually offered","route":"/technologies/rejuv-tx-long-term-follow-up-frameworks/"}],"target":[{"id":"bcma","kind":"target","name":"BCMA","route":"/targets/bcma/"},{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"},{"id":"cd28","kind":"target","name":"CD28","route":"/targets/cd28/"},{"id":"cd7","kind":"target","name":"CD7","route":"/targets/cd7/"},{"id":"cd70","kind":"target","name":"CD70","route":"/targets/cd70/"},{"id":"cldn18-2","kind":"target","name":"Claudin 18.2","route":"/targets/cldn18-2/"},{"id":"cldn6","kind":"target","name":"Claudin 6","route":"/targets/cldn6/"},{"id":"epcam","kind":"target","name":"EpCAM","route":"/targets/epcam/"},{"id":"gpc3","kind":"target","name":"Glypican-3","route":"/targets/gpc3/"},{"id":"gprc5d","kind":"target","name":"GPRC5D","route":"/targets/gprc5d/"},{"id":"il6","kind":"target","name":"Interleukin-6 and IL-6 receptor","route":"/targets/il6/"},{"id":"mesothelin","kind":"target","name":"Mesothelin","route":"/targets/mesothelin/"},{"id":"muc16","kind":"target","name":"MUC16 (CA-125)","route":"/targets/muc16/"}],"drug":[{"id":"anitocabtagene-autoleucel","kind":"drug","name":"Anitocabtagene autoleucel","route":"/drugs/anitocabtagene-autoleucel/"},{"id":"axicabtagene-ciloleucel","kind":"drug","name":"Axicabtagene ciloleucel","route":"/drugs/axicabtagene-ciloleucel/"},{"id":"brexucabtagene-autoleucel","kind":"drug","name":"Brexucabtagene autoleucel","route":"/drugs/brexucabtagene-autoleucel/"},{"id":"ciltacabtagene-autoleucel","kind":"drug","name":"Ciltacabtagene autoleucel","route":"/drugs/ciltacabtagene-autoleucel/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"emapalumab","kind":"drug","name":"Emapalumab","route":"/drugs/emapalumab/"},{"id":"equecabtagene-autoleucel","kind":"drug","name":"Equecabtagene autoleucel","route":"/drugs/equecabtagene-autoleucel/"},{"id":"fludarabine","kind":"drug","name":"Fludarabine","route":"/drugs/fludarabine/"},{"id":"idecabtagene-vicleucel","kind":"drug","name":"Idecabtagene vicleucel","route":"/drugs/idecabtagene-vicleucel/"},{"id":"inaticabtagene-autoleucel","kind":"drug","name":"Inaticabtagene autoleucel","route":"/drugs/inaticabtagene-autoleucel/"},{"id":"lisocabtagene-maraleucel","kind":"drug","name":"Lisocabtagene maraleucel","route":"/drugs/lisocabtagene-maraleucel/"},{"id":"nxc-201-car-t","kind":"drug","name":"NXC-201 CAR-T","route":"/drugs/nxc-201-car-t/"},{"id":"obecabtagene-autoleucel","kind":"drug","name":"Obecabtagene autoleucel","route":"/drugs/obecabtagene-autoleucel/"},{"id":"relmacabtagene-autoleucel","kind":"drug","name":"Relmacabtagene autoleucel","route":"/drugs/relmacabtagene-autoleucel/"},{"id":"satricabtagene-autoleucel","kind":"drug","name":"Satricabtagene autoleucel","route":"/drugs/satricabtagene-autoleucel/"},{"id":"talicabtagene-autoleucel","kind":"drug","name":"Talicabtagene autoleucel","route":"/drugs/talicabtagene-autoleucel/"},{"id":"tisagenlecleucel","kind":"drug","name":"Tisagenlecleucel","route":"/drugs/tisagenlecleucel/"},{"id":"tocilizumab","kind":"drug","name":"Tocilizumab","route":"/drugs/tocilizumab/"},{"id":"varnimcabtagene-autoleucel","kind":"drug","name":"Varnimcabtagene autoleucel","route":"/drugs/varnimcabtagene-autoleucel/"},{"id":"zevorcabtagene-autoleucel","kind":"drug","name":"Zevorcabtagene autoleucel","route":"/drugs/zevorcabtagene-autoleucel/"}],"company":[{"id":"adicet-bio","kind":"company","name":"Adicet Bio","route":"/companies/adicet-bio/"},{"id":"allogene","kind":"company","name":"Allogene Therapeutics","route":"/companies/allogene/"},{"id":"allotera-therapeutics","kind":"company","name":"Allotera Therapeutics (formerly Wugen)","route":"/companies/allotera-therapeutics/"},{"id":"arcellx","kind":"company","name":"Arcellx","route":"/companies/arcellx/"},{"id":"arsenal-bio","kind":"company","name":"Arsenal Biosciences","route":"/companies/arsenal-bio/"},{"id":"aurigene","kind":"company","name":"Aurigene Oncology","route":"/companies/aurigene/"},{"id":"bellicum","kind":"company","name":"Bellicum Pharmaceuticals","route":"/companies/bellicum/"},{"id":"cargo-therapeutics","kind":"company","name":"CARGO Therapeutics","route":"/companies/cargo-therapeutics/"},{"id":"caribou","kind":"company","name":"Caribou Biosciences","route":"/companies/caribou/"},{"id":"cartesian-therapeutics","kind":"company","name":"Cartesian Therapeutics","route":"/companies/cartesian-therapeutics/"},{"id":"cartx-therapeutics","kind":"company","name":"CARTx 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