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

The Melanoma-associated antigen 3-specific T-cell receptor (MAGE-A3 TCR) is a specialized immune receptor engineered to recognize and bind to MAGE-A3, a member of the cancer-testis antigen family (UniProt P43357) [3]. MAGE-A3 is an ideal therapeutic target because it is highly expressed in various cancers, such as melanoma and non-small cell lung cancer, but is absent from normal adult tissues except for the immune-privileged testis (NCI Thesaurus) [4]. These TCRs are typically introduced into a patient's CD8+ T-cells via viral vectors to create TCR-engineered T-cell (TCR-T) therapies. Once infused, the MAGE-A3 TCR recognizes specific MAGE-A3 peptide fragments presented by Human Leukocyte Antigen (HLA) molecules on the surface of tumor cells, leading to T-cell activation and the subsequent destruction of the cancer cell (Morgan et al., 2013) [1]. Despite their potential, MAGE-A3 TCRs have been associated with severe safety concerns, including lethal off-target cross-reactivity with the Titin protein in the heart and MAGE-A12 in the brain (Linette et al., 2013) [2]. Consequently, current research focuses on improving the specificity of these receptors to ensure they distinguish between the intended tumor antigen and similar proteins in healthy tissues.

Other names

MAGE-3-specific TCRMAGE-A3-specific CD8+ T-cell receptorAnti-MAGE-A3 TCRMAGE-A3-specific T-cell receptor

Engineered T-cell receptors recognize the MAGE-A3 peptide-HLA complex on the surface of cancer cells, triggering T-cell activation, cytokine release, and directed lysis of the target cell.