Human leukocyte antigen DP4 presenting melanoma-associated antigen 3 peptide (HLA-DP4/MAGE-A3)

The HLA-DP4 presenting MAGE-A3 peptide complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy. MAGE-A3 (Melanoma-associated antigen 3) is a cancer-testis antigen that is typically silent in normal adult tissues, except for the testis and placenta, but is frequently overexpressed in various malignancies including melanoma and lung cancer (UniProt P43357). HLA-DP4, specifically the HLA-DPB1*04:01 allele, is one of the most common MHC Class II molecules in Caucasian populations, making this complex a broadly applicable target (IMGT/HLA Database). When MAGE-A3 peptides, such as the 243-258 sequence, are processed and presented by HLA-DP4 on the surface of tumor cells, they can be recognized by specific T-cell receptors (TCRs) (PubMed: 23873058). Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies like KITE-718 and cancer vaccines designed to elicit a robust immune response (Gilead Sciences). Clinical development has focused on leveraging this target to treat solid tumors while minimizing off-target effects, though cross-reactivity with other MAGE proteins remains a safety consideration (PubMed: 23580853).

Other names

HLA-DPB1*04:01/MAGE-A3 complexMAGE-A3:243-258/HLA-DP4MAGE-A3/HLA-DP4MHC Class II-restricted MAGE-A3 antigen

T-cell receptor (TCR) recognition of the MAGE-A3 peptide presented by HLA-DP4 leads to the activation of CD4+ T cells, which provide help for CD8+ cytotoxic T cells and can also exert direct anti-tumor activity (PubMed: 23873058).