T-cell receptor recognizing patient-specific tumor peptide–MHC complexes (Neoantigen-specific TCR)

The T-cell receptor (TCR) recognizing patient-specific tumor peptide–MHC complexes is a specialized immune receptor used in personalized cancer immunotherapy (PubMed: 31578527). Unlike standard CAR-T cells that recognize surface proteins, these TCRs are engineered to detect intracellular proteins processed and presented as neoantigens on the cell surface by Major Histocompatibility Complex (MHC) molecules (Nature Reviews Drug Discovery, 2021). These neoantigens arise from unique somatic mutations within an individual patient's tumor, making the target highly specific to the malignancy and reducing the risk of attacking healthy tissues (Frontiers in Immunology, 2020). In TCR-T cell therapy, a patient's own T cells are isolated and genetically modified to express a high-affinity TCR specific to these neoantigens (ClinicalTrials.gov: NCT03970382). Once re-infused, these cells seek out and destroy tumor cells through direct cytotoxic activity and the release of pro-inflammatory cytokines. This approach is particularly promising for solid tumors, which often lack suitable surface-level targets but harbor numerous internal mutations.

Other names

Neoantigen-specific T-cell receptorTumor-specific T-cell receptorPersonalized TCRMutation-specific T-cell receptorNeoTCR

Adoptive cell transfer of T-cells engineered to express a TCR that specifically binds to a neoantigen-MHC complex, triggering T-cell activation, proliferation, and tumor cell lysis.