T-cell receptor recognizing MAGE-A3-derived peptide–MHC complexes (TCR-MAGE-A3)

The T-cell receptor (TCR) recognizing MAGE-A3-derived peptide–MHC complexes is a therapeutic receptor used in adoptive T-cell transfer (TCR-T) for cancer immunotherapy. MAGE-A3 (Melanoma-associated antigen 3) is a cancer-testis antigen that is highly expressed in various malignancies but restricted in normal tissues, making it an ideal target for redirected T-cell activity (Source: UniProt P43357). These engineered TCRs are designed to recognize MAGE-A3 peptides presented by specific Human Leukocyte Antigen (HLA) alleles, such as HLA-A*01 or HLA-A*02, on the surface of cancer cells. Upon recognition, the TCR-engineered T cells undergo activation and expansion, leading to the targeted destruction of tumor cells through the release of perforins, granzymes, and inflammatory cytokines. However, the clinical development of these TCRs has been complicated by severe off-target toxicities. Specifically, early trials reported fatalities due to TCR cross-reactivity with MAGE-A12 in the central nervous system and the muscle protein Titin in the heart, emphasizing the necessity for high-resolution specificity testing in TCR engineering (Source: PubMed PMID: 23908460, 23580678).

Other names

MAGE-A3-specific T-cell receptorMAGE-3 TCRAnti-MAGE-A3 TCRHLA-A*01-restricted MAGE-A3 TCRHLA-A*02-restricted MAGE-A3 TCRTCR-MAGE-A3

Engineered T-cell receptors bind to specific MAGE-A3 peptide fragments (e.g., EVDPIGHLY or KVAELVHFL) presented by HLA molecules on tumor cells, triggering a cytotoxic immune response and tumor cell lysis (Source: PubMed PMID: 23908460, 23580678).