A cell therapy that engineers a patient's T cells to express a chosen T-cell receptor — including ones that recognize neoantigens — then infuses them to attack the tumor.
TCR-T cell therapy is a form of adoptive cell transfer. Rather than teaching the immune system to make its own response — what a vaccine does — it manufactures the response directly: T cells are taken from the patient, engineered to express a specific T-cell receptor (TCR) that recognizes a chosen tumor target, expanded to large numbers, and infused back after lymphodepletion.
Unlike CAR-T, which recognizes whole proteins on the cell surface, a TCR sees short peptides presented on HLA molecules — the same peptide-MHC complexes that neoantigen prediction is all about. That means TCR-T can target intracellular proteins, including mutated ones, which makes neoantigens accessible to it. The trade-off is HLA restriction: a given TCR only works for patients carrying the matching HLA allele.
For the neoantigen field, TCR-T is the sibling of the vaccine. Both depend on identifying which mutated peptide is presented and recognizable; they differ only in delivery — coax the patient's T cells (vaccine) versus build and infuse them (TCR-T). ASCO 2026's NT-175, an engineered TCR-T against the TP53 R175H neoantigen, brought the first clinical responses for this approach against a shared neoantigen.
TCR-T (T-cell-receptor-engineered T-cell therapy) is a treatment that takes a patient's T cells, engineers them to express a T-cell receptor recognizing a specific tumor target, expands them, and infuses them back. Because a TCR recognizes peptides presented on HLA, TCR-T can target intracellular and mutated proteins — including neoantigens.
CAR-T uses a synthetic receptor that binds whole proteins on the cell surface, so it is limited to surface targets but is not HLA-restricted. TCR-T uses a natural T-cell receptor that recognizes short peptides presented on HLA, so it can reach intracellular and mutated proteins (like neoantigens) but only works in patients with the matching HLA allele.
Both target neoantigens and share the same upstream step of predicting which mutated peptides are presented. A vaccine is active immunization — the patient raises the T-cell response. TCR-T is adoptive transfer — the T cells are engineered and infused ready-made. Vaccines are lighter to make and hit many targets; TCR-T delivers a defined dose of high-avidity cells but is complex, usually single-target, and HLA-restricted.