Melanoma-associated antigen 3 (MAGE-A3) epitope 161-180 (MAGE-A3 (161-180))

Melanoma-associated antigen 3 (MAGE-A3) epitope 161-180 is a 20-amino acid peptide sequence (VFGIELMEVDPIGHLYIFAT) derived from the MAGE-A3 protein, a prominent member of the cancer-testis antigen family (UniProt P43357) [2.2.2, 3.2.1]. MAGE-A3 is highly expressed in various malignancies, such as melanoma and non-small cell lung cancer, but is restricted to the testes and placenta in healthy adults, making it an ideal target for cancer immunotherapy [2.2.1, 2.2.5]. This specific epitope is a "long peptide" that contains multiple nested T-cell recognition sites, most notably the HLA-A*01-restricted CD8+ epitope (168-176, EVDPIGHLY) and a promiscuous HLA-DP4-restricted CD4+ epitope [2.3.1, 3.2.1]. It is primarily targeted in cancer immunotherapy through vaccine platforms, such as PeptiCRAd-1 and recombinant protein formulations like GSK1572932A, which aim to elicit a robust and coordinated immune response [2.1.4, 3.2.1]. By presenting these fragments to the immune system, the therapy seeks to activate both helper and cytotoxic T lymphocytes to recognize and destroy MAGE-A3-positive tumor cells [2.2.3, 3.1.5]. Despite its high immunogenicity, clinical trials for MAGE-A3-targeted vaccines have struggled to meet primary endpoints in large-scale phase III studies, such as the MAGRIT and DERMA trials [2.1.1, 2.1.2]. Furthermore, the development of affinity-enhanced T-cell receptors against the 168-176 sequence within this epitope has revealed critical safety risks, including fatal cardiac toxicity due to cross-recognition of the muscle protein Titin [2.3.4, 2.3.5].

Other names

MAGE-3 161-180MAGE-A3 p161-180VFGIELMEVDPIGHLYIFATMAGE-A3 161-180 peptide

Active immunotherapy via vaccination to stimulate MAGE-A3-specific CD4+ and CD8+ T-cell responses.