# TCR-T cell therapy

Source: https://onco.cc/technologies/tcr-t/  
OnCo record `tcr-t` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Technology
- Status: approved
- Last checked: 2026-09-04
- Principle: Transgenic αβ TCR recognises a peptide-HLA complex; restricted to patients with the matching HLA allele.
- Since: 2024
- Strengths: Intracellular targets (cancer-testis antigens, neoantigens)
- Limitations: HLA restriction; Cross-reactivity risk; Antigen presentation loss as escape

## Sources

- ClinicalTrials.gov NCT03967223: IGNYTE-ESO: https://clinicaltrials.gov/study/NCT03967223

## Connected records

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

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