{"entity":{"id":"tcr-t","kind":"technology","name":"TCR-T cell therapy","aka":[],"tldr":"T cells engineered with a receptor that sees fragments of proteins inside the cancer cell, reaching targets CAR-T cannot.","summary":"Afamitresgene autoleucel (Tecelra) was the first approved TCR-T, for MAGE-A4+ HLA-A*02+ synovial sarcoma (2024, label expanded 2026). Letetresgene (NY-ESO-1) followed in trials. Neoantigen-specific TCR-T against KRAS G12D and TP53 hotspots (NCI Rosenberg) and PRAME-directed TCR-T (Immatics IMA203, phase 3 in melanoma) are the most watched.","status":"approved","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03967223: IGNYTE-ESO","url":"https://clinicaltrials.gov/study/NCT03967223"}],"tags":[],"related":[],"cancers":["sarcoma","melanoma"],"sections":["cell-therapy"],"technologies":[],"targets":["mage-a4","gp100","kras","tp53"],"drugs":["afamitresgene-autoleucel"],"companies":["affini-t-therapeutics","neogene-therapeutics","invocata","alaunos","medigene","anocca"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["apheresis-starting-material","viral-vector-manufacturing","cell-therapy-cold-chain","cell-therapy-release-testing"],"notes":[],"principle":"Transgenic αβ TCR recognises a peptide-HLA complex; restricted to patients with the matching HLA allele.","strengths":["Intracellular targets (cancer-testis antigens, neoantigens)"],"limitations":["HLA restriction","Cross-reactivity risk","Antigen presentation loss as escape"],"since":2024},"route":"/technologies/tcr-t/","neighbours":{"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"merkel-cell-carcinoma","kind":"cancer","name":"Merkel cell carcinoma","route":"/cancers/merkel-cell-carcinoma/"},{"id":"nasopharyngeal","kind":"cancer","name":"Nasopharyngeal carcinoma","route":"/cancers/nasopharyngeal/"},{"id":"recurrent-metastatic-nasopharyngeal-carcinoma","kind":"cancer","name":"Recurrent and metastatic nasopharyngeal carcinoma","route":"/cancers/recurrent-metastatic-nasopharyngeal-carcinoma/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"section":[{"id":"cell-therapy","kind":"section","name":"Cell Therapy","route":"/fronts/cell-therapy/"}],"target":[{"id":"gp100","kind":"target","name":"gp100 (PMEL)","route":"/targets/gp100/"},{"id":"hla-a","kind":"target","name":"HLA-A","route":"/targets/hla-a/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"mage-a4","kind":"target","name":"MAGE-A4","route":"/targets/mage-a4/"},{"id":"prame","kind":"target","name":"PRAME","route":"/targets/prame/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"drug":[{"id":"afamitresgene-autoleucel","kind":"drug","name":"Afamitresgene autoleucel","route":"/drugs/afamitresgene-autoleucel/"},{"id":"letetresgene-autoleucel","kind":"drug","name":"Letetresgene autoleucel","route":"/drugs/letetresgene-autoleucel/"},{"id":"tac01-cldn18-2","kind":"drug","name":"TAC01-CLDN18.2","route":"/drugs/tac01-cldn18-2/"},{"id":"tebentafusp","kind":"drug","name":"Tebentafusp","route":"/drugs/tebentafusp/"}],"company":[{"id":"affini-t-therapeutics","kind":"company","name":"Affini-T Therapeutics","route":"/companies/affini-t-therapeutics/"},{"id":"alaunos","kind":"company","name":"Alaunos Therapeutics (formerly Ziopharm Oncology)","route":"/companies/alaunos/"},{"id":"anocca","kind":"company","name":"Anocca","route":"/companies/anocca/"},{"id":"immatics","kind":"company","name":"Immatics","route":"/companies/immatics/"},{"id":"invocata","kind":"company","name":"Invocata","route":"/companies/invocata/"},{"id":"medigene","kind":"company","name":"Medigene","route":"/companies/medigene/"},{"id":"neogene-therapeutics","kind":"company","name":"Neogene Therapeutics","route":"/companies/neogene-therapeutics/"},{"id":"takara-bio","kind":"company","name":"Takara Bio","route":"/companies/takara-bio/"},{"id":"tscan","kind":"company","name":"TScan Therapeutics","route":"/companies/tscan/"}],"technology":[{"id":"apheresis-starting-material","kind":"technology","name":"Apheresis and starting-material collection","route":"/technologies/apheresis-starting-material/"},{"id":"cell-therapy-release-testing","kind":"technology","name":"Cell-therapy release and potency testing","route":"/technologies/cell-therapy-release-testing/"},{"id":"cell-therapy-cold-chain","kind":"technology","name":"Cryopreservation and cell-therapy cold chain","route":"/technologies/cell-therapy-cold-chain/"},{"id":"viral-vector-manufacturing","kind":"technology","name":"Viral vector manufacturing (lentiviral, retroviral, AAV)","route":"/technologies/viral-vector-manufacturing/"}],"term":[{"id":"hla-a02-restriction","kind":"term","name":"HLA-A*02:01 restriction","route":"/terms/hla-a02-restriction/"},{"id":"neoantigen","kind":"term","name":"Neoantigen","route":"/terms/neoantigen/"},{"id":"t-cell","kind":"term","name":"T cell","route":"/terms/t-cell/"}],"idea":[{"id":"idea-bio1-pmhc-bispecifics-public-drivers","kind":"idea","name":"Antibodies that see mutant KRAS and p53 fragments displayed on the cell surface","route":"/ideas/idea-bio1-pmhc-bispecifics-public-drivers/"},{"id":"idea-moon-engineered-immune-surveillance","kind":"idea","name":"Engineered immune surveillance: long-lived programmed immune cells that patrol for early cancer","route":"/ideas/idea-moon-engineered-immune-surveillance/"},{"id":"idea-tcr-t-beyond-hla-a2","kind":"idea","name":"Extending sarcoma TCR-T beyond HLA-A*02","route":"/ideas/idea-tcr-t-beyond-hla-a2/"},{"id":"idea-fund-hospital-exemption-registry","kind":"idea","name":"Hospital-exemption cell therapies at scale, backed by a shared registry","route":"/ideas/idea-fund-hospital-exemption-registry/"},{"id":"idea-reg-public-cell-therapy-foundries","kind":"idea","name":"Public cell-therapy foundries at cancer centres for academics and start-ups","route":"/ideas/idea-reg-public-cell-therapy-foundries/"},{"id":"idea-splice-neoantigens","kind":"idea","name":"Shared splice-derived neoantigens as off-the-shelf vaccine targets","route":"/ideas/idea-splice-neoantigens/"},{"id":"idea-prame-tcr-beyond-a02","kind":"idea","name":"TCR therapeutics for non-HLA-A*02 patients","route":"/ideas/idea-prame-tcr-beyond-a02/"},{"id":"idea-neoantigen-immunogenicity-rules","kind":"idea","name":"What makes a neoantigen actually immunogenic?","route":"/ideas/idea-neoantigen-immunogenicity-rules/"}],"trial":[{"id":"ignyte-eso","kind":"trial","name":"IGNYTE-ESO","route":"/trials/ignyte-eso/"},{"id":"nct04044768","kind":"trial","name":"Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma","route":"/trials/nct04044768/"},{"id":"nct05642455","kind":"trial","name":"SPEARHEAD-3 Pediatric Study","route":"/trials/nct05642455/"},{"id":"nct05862324","kind":"trial","name":"TAC T-cells for the Treatment of Claudin 18.2 Positive Solid Tumors (TACTIC-3)","route":"/trials/nct05862324/"},{"id":"nct05549297","kind":"trial","name":"Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)","route":"/trials/nct05549297/"}],"institution":[{"id":"ccc-tuebingen","kind":"institution","name":"Comprehensive Cancer Center Tübingen-Stuttgart","route":"/institutions/ccc-tuebingen/"},{"id":"san-raffaele","kind":"institution","name":"IRCCS Ospedale San Raffaele","route":"/institutions/san-raffaele/"},{"id":"chuv-lausanne","kind":"institution","name":"Lausanne University Hospital (CHUV) / Ludwig Institute Lausanne","route":"/institutions/chuv-lausanne/"},{"id":"mdc-berlin","kind":"institution","name":"Max Delbrück Center for Molecular Medicine","route":"/institutions/mdc-berlin/"},{"id":"nci","kind":"institution","name":"National Cancer Institute (NIH)","route":"/institutions/nci/"},{"id":"nci-ccr","kind":"institution","name":"NCI Center for Cancer Research (intramural programme)","route":"/institutions/nci-ccr/"},{"id":"oslo-radium-hospital","kind":"institution","name":"Oslo University Hospital, The Norwegian Radium Hospital","route":"/institutions/oslo-radium-hospital/"},{"id":"qimr-berghofer","kind":"institution","name":"QIMR Berghofer Medical Research Institute","route":"/institutions/qimr-berghofer/"},{"id":"rutgers-cinj","kind":"institution","name":"Rutgers Cancer Institute of New Jersey","route":"/institutions/rutgers-cinj/"},{"id":"maryland-greenebaum","kind":"institution","name":"University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center","route":"/institutions/maryland-greenebaum/"}],"roadmap":[{"id":"cell-therapy-roadmap","kind":"roadmap","name":"Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR","route":"/roadmaps/cell-therapy-roadmap/"},{"id":"kras-roadmap","kind":"roadmap","name":"KRAS roadmap: undruggable → G12C → pan-RAS","route":"/roadmaps/kras-roadmap/"}],"person":[{"id":"antoni-ribas","kind":"person","name":"Antoni Ribas","route":"/people/antoni-ribas/"},{"id":"patrick-hwu","kind":"person","name":"Patrick Hwu","route":"/people/patrick-hwu/"},{"id":"philip-greenberg","kind":"person","name":"Philip D. Greenberg","route":"/people/philip-greenberg/"},{"id":"sandra-dangelo","kind":"person","name":"Sandra P. D'Angelo","route":"/people/sandra-dangelo/"},{"id":"steven-rosenberg","kind":"person","name":"Steven A. Rosenberg","route":"/people/steven-rosenberg/"},{"id":"ton-schumacher","kind":"person","name":"Ton Schumacher","route":"/people/ton-schumacher/"},{"id":"lu-you","kind":"person","name":"You Lu","route":"/people/lu-you/"}],"bottleneck":[{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"}],"pathway":[{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","route":"/pathways/antigen-presentation-immunoediting/"},{"id":"oncogenic-viruses","kind":"pathway","name":"Oncogenic viruses","route":"/pathways/oncogenic-viruses/"}],"paper":[{"id":"paper-spearhead-1-lancet-2024","kind":"paper","name":"SPEARHEAD-1: afamitresgene autoleucel, the first engineered T-cell receptor therapy approved for a solid tumour, in synovial sarcoma","route":"/key-papers/paper-spearhead-1-lancet-2024/"}]}}