Melanoma Antigen Family A, 3 (MAGE-A3) is a member of the melanoma-associated antigen (MAGE) family, which is a group of proteins encoded by genes located on the X chromosome. These proteins are known for their restricted expression pattern, being primarily found in male germ cells and various types of tumors, but not in normal tissues .
The MAGE-A3 gene is located on the Xq28 region of the X chromosome. It is part of a cluster of MAGE genes that share a high degree of sequence similarity. The MAGE-A3 protein consists of 314 amino acids and has a molecular weight of approximately 36 kDa . The protein is characterized by the presence of a conserved MAGE homology domain, which is crucial for its function .
MAGE-A3 is predominantly expressed in a variety of cancers, including melanoma, non-small cell lung cancer, and hematologic malignancies . Its expression in normal tissues is limited to immune-privileged sites such as the testis, which prevents it from being targeted by the immune system under normal conditions . The exact physiological function of MAGE-A3 in healthy cells remains unclear, but it is believed to play a role in cell cycle regulation and apoptosis .
The restricted expression pattern of MAGE-A3 makes it an attractive target for cancer immunotherapy. MAGE-A3 is presented on the surface of tumor cells by MHC class I molecules, making it recognizable by cytotoxic T lymphocytes . This has led to the development of various therapeutic strategies, including cancer vaccines and adoptive T-cell transfer therapies .
One notable example is the development of a cancer vaccine by GlaxoSmithKline, which targets MAGE-A3. This vaccine is a fusion protein of MAGE-A3 and Haemophilus influenzae protein D, combined with a proprietary immunoadjuvant . Clinical trials have shown promising results, with the vaccine inducing a robust immune response in patients with MAGE-A3-positive tumors .