Melanoma-associated antigen 3 (MAGE-A3) peptide YMDGTMSQV-specific T-cell receptor (MAGE-A3 TCR)

The CD8+ T-cell receptor (TCR) specific for the MAGE-A3 peptide YMDGTMSQV (residues 271-279) presented by HLA-A*02:01 is a therapeutic target used in adoptive cell therapies for cancer. MAGE-A3 is a cancer-testis antigen frequently overexpressed in melanoma, non-small cell lung cancer, and other solid tumors, while being restricted in normal tissues, which provides a favorable therapeutic window (PMID: 24608573). This TCR allows engineered T cells to recognize and kill tumor cells by binding to the peptide-MHC complex on the cell surface. Plasmacytoid dendritic cells (pDCs) play a crucial role in this context as specialized antigen-presenting cells that can effectively prime and activate these MAGE-A3-specific CD8+ T cells, often utilized in therapeutic vaccine strategies (PMID: 23407548). Despite its potential, the development of MAGE-A3 TCRs has been complicated by severe safety issues, including fatal cross-reactivity with the cardiac protein Titin and the neural protein MAGE-A12 (PMID: 23943877, PMID: 23558281). Consequently, modern drug development, such as the KITE-718 program, emphasizes rigorous screening for off-target effects to ensure high specificity. These therapies represent a personalized approach to oncology, requiring patients to be screened for both HLA-A*02:01 positivity and MAGE-A3 expression.

Other names

MAGE-A3 271-279 TCRHLA-A*02:01/MAGE-A3 TCRMAGE-A3-specific CD8+ T-cell receptorMAGE-A3/HLA-A2 TCR

Adoptive T-cell therapy involving the engineering of patient T cells to express a TCR specific for the MAGE-A3 peptide-MHC complex, leading to targeted lysis of tumor cells.