T cell receptor recognizing MAGE-A3 peptide–HLA complex (MAGE-A3 TCR) (MAGE-A3 TCR)

The T cell receptor (TCR) recognizing MAGE-A3 peptide–HLA complexes is a therapeutic receptor used in engineered T-cell therapies (TCR-T) to treat various malignancies. MAGE-A3 (Melanoma-associated antigen 3) is a cancer-testis antigen that is highly expressed in tumors such as melanoma and non-small cell lung cancer, but is generally absent in normal tissues, making it a promising target for immunotherapy (van der Bruggen et al., Science, 1991). These TCRs are engineered to recognize MAGE-A3 peptides presented by specific Human Leukocyte Antigen (HLA) molecules, including HLA class I (e.g., HLA-A*01, HLA-A*02) and HLA class II (e.g., HLA-DPB1*04) (Yao et al., J Immunother, 2016). Upon binding to the peptide-HLA complex, the TCR triggers T-cell activation and the subsequent lysis of the tumor cell. However, the development of MAGE-A3 TCRs has faced significant safety hurdles due to off-target toxicities. Clinical trials have reported fatal adverse events, including encephalopathy caused by cross-reactivity with MAGE-A12 in the brain (Morgan et al., J Clin Oncol, 2013) and cardiotoxicity due to cross-reactivity with the muscle protein Titin (Linette et al., Blood, 2013). Current research, such as the KITE-718 program, focuses on improving TCR specificity to mitigate these risks while maintaining anti-tumor efficacy (ClinicalTrials.gov, NCT03159585).

Other names

MAGE-A3-specific T-cell receptorMAGE-A3 TCRTCR-MAGE-A3Anti-MAGE-A3 TCRMAGE-A3-specific TCR

Adoptive T-cell therapy using T cells engineered to express a T-cell receptor (TCR) specific for MAGE-A3 peptides presented by HLA molecules, leading to MHC-restricted tumor cell recognition and lysis.