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

The HLA-DP4 presenting MAGE-A3-derived epitopes complex is a molecular target composed of the Human Leukocyte Antigen (HLA) Class II molecule DP4 (primarily the DPB1*04:01 allele) and a peptide fragment from the Melanoma-associated antigen 3 (MAGE-A3) (Schultz et al., 2000). MAGE-A3 is a member of the cancer-testis antigen family, which is typically expressed during embryonic development and in the adult testis but is aberrantly re-expressed in a wide range of cancers, including melanoma, non-small cell lung cancer, and bladder cancer (Gure et al., 2005). Because the testis is an immune-privileged site, MAGE-A3 is an ideal target for immunotherapy as its expression on tumor cells can be recognized by the immune system without significant damage to healthy tissues. The HLA-DP4/MAGE-A3 complex is specifically recognized by CD4+ T-cell receptors, making it a focal point for the development of T-cell receptor (TCR) engineered T-cell therapies like GSK3845097 (NCT02111850). These therapies aim to harness the patient's immune system to selectively kill tumor cells presenting this specific epitope. Given that HLA-DP4 is one of the most prevalent HLA Class II alleles in the human population, appearing in approximately 75% of Caucasians, this target offers a broad therapeutic window for patients across various ethnic backgrounds (Mack et al., 2013).

Other names

MAGE-A3:HLA-DPB1*04:01 complexMAGE-A3/HLA-DP4MAGE-A3 peptide-MHC class II complexHLA-DPB1*04:01-restricted MAGE-A3 epitope

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and tumor cell lysis.