Melanoma-associated antigen 4 (MAGE-A4) (MAGE-A4)

Melanoma-associated antigen 4 (MAGE-A4) is a member of the cancer-testis antigen (CTA) family, characterized by its restricted expression in immune-privileged germline tissues and its aberrant over-expression in various solid tumors [1, 2]. Biologically, MAGE-A4 functions as a component of E3 ubiquitin ligase complexes, notably interacting with TRIM28 to facilitate the degradation of the tumor suppressor p53, thereby inhibiting apoptosis and promoting cell cycle progression [8]. It also plays a role in DNA damage repair by stabilizing RAD18 and recruiting Y-family DNA polymerases, which enhances the survival of cancer cells under genotoxic stress [5, 8]. Due to its high tumor specificity and lack of expression in normal somatic tissues, MAGE-A4 is a premier target for T-cell receptor (TCR) engineered T-cell therapies and bispecific T-cell engagers [2, 7]. The clinical significance of MAGE-A4 was highlighted by the FDA approval of afamitresgene autoleucel (Afami-cel), the first TCR-T therapy for synovial sarcoma, which targets MAGE-A4 peptides presented by HLA-A*02 molecules [10, 13].

Other names

MAGE4MAGE-4Melanoma antigen family A member 4Cancer/testis antigen 1.4CT1.4MAGEA4

T-cell receptor (TCR) mediated cytotoxicity, bispecific T-cell engagement, and induction of apoptosis through p53 pathway modulation.