TCR-T cell therapy
T cells engineered with a receptor that sees fragments of proteins inside the cancer cell, reaching targets CAR-T cannot.
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.
How it works
Transgenic αβ TCR recognises a peptide-HLA complex; restricted to patients with the matching HLA allele.
- Intracellular targets (cancer-testis antigens, neoantigens)
- HLA restriction
- Cross-reactivity risk
- Antigen presentation loss as escape
Afamitresgene autoleucel was the first engineered T-cell receptor therapy approved for a solid tumour, synovial sarcoma.
Letetresgene autoleucel is a second engineered T-cell receptor therapy for sarcoma, targeting NY-ESO-1 in synovial sarcoma and myxoid/round cell liposarcoma; a BLA is expected by the end of 2026.
The first drug to improve survival in metastatic uveal melanoma, and the first TCR-based bispecific.
Afami-cel showed that T cells can be redirected against an intracellular cancer antigen, something CAR-T cannot do, and produced meaningful responses in a rare sarcoma with few options. It opens a path to TCR-T against other shared antigens and neoantigens. Restriction to one HLA type and one antigen, plus complex manufacturing, means it will help a small, defined group.
Patients with advanced synovial sarcoma, a rare cancer of young adults with few effective drugs, now have an approved cell therapy that produces responses lasting about a year in a substantial minority, if their tissue type and tumour antigen match. It proves that engineered T cells can work against a solid tumour when a good target is present, which had been elusive. It is not a cure for most, requires specialised centres, and only a minority of patients are eligible.
Latest papers
topQuery for this technology: (TITLE:"TCR-T" OR ABSTRACT:"TCR-T" OR TITLE:"T cell receptor therapy" OR ABSTRACT:"T cell receptor therapy" OR TITLE:"TCR-engineered T cells" OR ABSTRACT:"TCR-engineered T cells"). Results are unfiltered search hits about TCR-T cell therapy, not a curated reading list.
Pages like this
not linked directly; found by shared links- TechnologyTIL therapy
Shares Public cell-therapy foundries at cancer centres for academics and start-ups, Patrick Hwu, Steven A. Rosenberg, Hospital-exemption cell therapies at scale, backed by a shared registry.
- ProductBrenetafusp
Shares TCR therapeutics for non-HLA-A*02 patients, HLA-A*02:01 restriction, PRAME, Tebentafusp.
- CompanyAdaptimmune
Shares SPEARHEAD-1: afami-cel, the first engineered T-cell receptor therapy approved for a solid tumour, in synovial sarcoma, Afamitresgene autoleucel, SPEARHEAD-1: afamitresgene autoleucel, the first engineered T-cell receptor therapy approved for a solid tumour, in synovial sarcoma, Sarcomas (soft tissue, bone, GIST).
- TechnologyT-cell engagers (bispecific)
Shares TCR therapeutics for non-HLA-A*02 patients, gp100 (PMEL), HLA-A*02:01 restriction, Antibodies that see mutant KRAS and p53 fragments displayed on the cell surface.
- CancerUveal melanoma
Shares gp100 (PMEL), HLA-A*02:01 restriction, PRAME, Tebentafusp.
- CompanyImmunocore
Shares Antibodies that see mutant KRAS and p53 fragments displayed on the cell surface, PRAME, Tebentafusp, Melanoma.
- Key paperC-144-01: lifileucel, tumour-infiltrating lymphocytes grown from a patient's own tumour, in melanoma after checkpoint inhibitors have failed
Shares SPEARHEAD-1: afami-cel, the first engineered T-cell receptor therapy approved for a solid tumour, in synovial sarcoma, Steven A. Rosenberg, Manufacturing cost and time for living and radioactive medicines, National Cancer Institute (NIH).
- TechnologyCAR-NK & CAR-macrophage
Shares Engineered immune surveillance: long-lived programmed immune cells that patrol for early cancer, QIMR Berghofer Medical Research Institute, Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR, Antigen presentation & immune editing.