Melanoma-associated antigen 1 peptide presented by HLA-A*02:01 (MAGE-A1/HLA-A*02:01)

The MAGE-A1 peptide presented by HLA-A*02:01 is a tumor-specific antigen complex that serves as a key target for adoptive T-cell therapies (Immatics, 2024; T-knife Therapeutics, 2022). MAGE-A1 (Melanoma-associated antigen 1) is a member of the cancer-testis antigen family, which is typically expressed in various cancers but restricted to the immune-privileged testis in healthy adults (Immatics, 2024; Pascolo et al., 2001). The specific epitope KVLEYVIKV, spanning residues 278-286 of the MAGE-A1 protein, is processed and displayed on the cell surface by the HLA-A*02:01 major histocompatibility complex (MHC) Class I molecule (Chaux et al., 1999; Cosmo Bio USA). Because the testis lacks MHC Class I expression, this peptide-MHC complex is essentially absent from normal tissues, providing a high degree of tumor specificity (Immatics, 2024). Therapeutic interventions, such as TCR-engineered T-cell (TCR-T) therapies like IMA202 and TK-8001, utilize synthetic T-cell receptors to recognize this complex and induce the lysis of malignant cells (Immatics, 2024; T-knife Therapeutics, 2022). These therapies are currently being evaluated in clinical trials for patients with HLA-A*02:01-positive solid tumors, including melanoma, hepatocellular carcinoma, and non-small cell lung cancer (Immatics, 2024; T-knife Therapeutics, 2022). The primary mechanism of action involves the redirection of cytotoxic T lymphocytes to identify and destroy cells presenting the MAGE-A1/HLA-A*02:01 complex (Chaux et al., 1999; Immatics, 2024). Safety monitoring is critical in these treatments to manage potential cytokine release syndrome and ensure no cross-reactivity with similar peptides in vital organs (Immatics, 2024; Linette et al., 2013).

Other names

MAGE-A1(278-286)/HLA-A*02:01KVLEYVIKV/HLA-A*02:01 complexMAGE-A1-HLA-A2 complexMelanoma-associated antigen 1/HLA-A*02:01CT1.1/HLA-A*02:01

T-cell receptor (TCR) mediated recognition and lysis of tumor cells