Melanoma-associated antigen 1 peptide-Human leukocyte antigen complex (MAGEA1-HLA complex) (MAGEA1-HLA)

The Melanoma-associated antigen 1 (MAGEA1) peptide-Human leukocyte antigen (HLA) complex is a specific molecular target formed by the presentation of intracellularly processed MAGEA1 fragments on the cell surface via HLA Class I molecules, most commonly HLA-A*01:01 (UniProt: P43355). MAGEA1 belongs to the cancer-testis antigen (CTA) family, meaning its expression is typically restricted to the immune-privileged environment of the testes in healthy individuals but is aberrantly upregulated in various malignancies, including melanoma and lung cancer (PubMed: 1844278). This restricted expression profile makes the MAGEA1-HLA complex an ideal target for immunotherapy, as it minimizes the risk of on-target, off-tumor toxicity. Therapeutic strategies targeting this complex primarily involve T-cell receptor (TCR) based approaches, such as TCR-engineered T cells (TCR-T) or bispecific T-cell engagers, which are designed to recognize the specific peptide-HLA interface with high affinity (Immatics, 2023). Upon binding, these therapies trigger a potent cytotoxic immune response against the tumor cells. Clinical development of drugs like IMA201 focuses on patients who are both HLA-A*01 positive and whose tumors express the MAGEA1 protein (ClinicalTrials.gov: NCT04756024).

Other names

MAGE-1 peptide-MHC complexMAGEA1-HLA-A*01 complexMelanoma antigen family A 1 peptide-HLA complexEADPTGHSY-HLA-A*01:01 complex

T-cell receptor (TCR) mediated recognition and subsequent cytotoxic T-lymphocyte (CTL) activation leading to tumor cell lysis.