T-cell receptor recognizing MAGE-A3 peptide-HLA-A*02:01 complex (MAGE-A3/HLA-A2 TCR)

The T-cell receptor (TCR) recognizing the MAGE-3.1/HLA-A2 complex is a specialized immune receptor targeted in the development of adoptive T-cell therapies for cancer. MAGE-A3 (Melanoma-associated antigen 3) is a cancer-testis antigen that is highly expressed in various malignancies, such as melanoma and non-small cell lung cancer, but absent in normal adult tissues except for the testes, making it an ideal tumor-specific target (UniProt P43357). The TCR is designed to recognize a specific 9-amino acid peptide from MAGE-A3 (FLWGPRALV, also known as MAGE-3.1) when it is presented on the cell surface by the HLA-A*02:01 major histocompatibility complex (Linette et al., 2013). Therapeutic strategies, such as KITE-718, involve engineering a patient's T cells to express this TCR to facilitate the targeted destruction of tumor cells (Kite Pharma, 2021). Despite its potential, this target has been associated with severe safety challenges; early clinical trials were halted after some TCRs showed lethal off-target toxicities due to cross-reactivity with the Titin protein in the heart and MAGE-A12 in the brain (Morgan et al., 2013; Linette et al., 2013). Consequently, modern development focuses on enhancing TCR specificity to avoid off-target effects while maintaining high affinity for the MAGE-A3/HLA-A2 complex.

Other names

MAGE-3 TCRMAGE-A3 TCRHLA-A*02:01-restricted MAGE-A3 T-cell receptorTCR-MAGE-A3MAGE-A3/HLA-A2 TCR

Adoptive cell transfer of T cells engineered to express a specific T-cell receptor (TCR) that recognizes the MAGE-A3 peptide presented by HLA-A*02:01, leading to MHC-restricted targeted destruction of MAGE-A3-positive tumor cells.