Melanoma-associated antigen A3 peptide–HLA-A*01:01 complex (MAGE-A3/HLA-A*01:01)

The target is a specific peptide-major histocompatibility complex (pMHC) consisting of a fragment of the Melanoma-associated antigen A3 (MAGE-A3) protein presented by the HLA-A*01:01 molecule. MAGE-A3 is a well-characterized cancer-testis antigen (CTA) that is highly expressed in various solid tumors, including melanoma, non-small cell lung cancer, and head and neck cancers, but is absent from healthy adult tissues except for the testis and placenta [1, 2]. Since these germline tissues lack MHC Class I expression, the MAGE-A3 peptide-MHC complex serves as a highly specific neoantigen-like target for immunotherapy [4]. IOV-2001 is an investigational adoptive T-cell therapy utilizing engineered T-cell receptors (TCRs) designed to recognize this pMHC complex with high affinity, leading to the activation of cytotoxic T lymphocytes and the subsequent destruction of tumor cells [1]. The therapeutic application of this target requires patients to be HLA-A*01:01 positive and have tumors that express the MAGE-A3 protein. A significant challenge in targeting this complex is the potential for TCR cross-reactivity with similar peptides from other MAGE family members or unrelated proteins in vital organs, which has historically led to severe adverse events in related clinical trials [5].

Other names

MAGE-A3/HLA-A1MAGE-A3:168-176/HLA-A*01:01MAGE-A3 pMHCEVDPIGHLY/HLA-A*01:01Antigen isolated from antigen-presenting cells recognized by T-cells 1

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