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Melanoma-associated antigen A4 peptide presented by HLA-A*02:01 (MAGE-A4/HLA-A*02:01 complex)
- Target
- MAGE-A4/HLA-A*02:01 complex
- Molecular classification
- Peptide–major histocompatibility complex class I complex, Tumor-associated antigen (cancer/testis antigen), Antigenic epitope
01
Overview
The “MAGE-A4 peptide presented by HLA-A*02:01” is a cell surface antigenic complex formed when tumor cells expressing the cancer/testis antigen Melanoma-associated antigen A4 (MAGE-A4) intracellularly process the protein into short peptides, most notably the 230-239 peptide “GVYDGREHTV.” This peptide epitope is then bound by the human leukocyte antigen-A*02:01 (HLA-A*02:01) molecule and displayed on the surface for recognition by cytotoxic T lymphocytes. Therapeutic strategies engineer TCRs or CAR-Ts to specifically recognize this complex, enabling selective killing of MAGE-A4-positive, HLA-A*02:01-positive cancer cells. This approach has led to FDA-approved therapies such as afamitresgene autoleucel for synovial sarcoma and is being evaluated for other solid tumors.
- Other names
- MAGE-A4/HLA-A2 complexMAGE-A4 peptide-HLA-A*02:01MAGE-A4 230-239 peptide presented by HLA-A*02:01 (“GVYDGREHTV”)Cancer/testis antigen MAGE-A4 epitope/HLA-A*02:01
02
Mechanism of action
Recognition of cancer cells presenting the MAGE-A4 peptide/HLA-A*02:01 complex by engineered high-affinity TCR or CAR-T cells, leading to cytotoxicity (tumor cell lysis) via T cell activation
03
Biological functions
Immune response (activates cytotoxic T lymphocytes)Cell recognition and targeting by engineered T cells
04
Disease associations
Cancer (notably synovial sarcoma, myxoid/round cell liposarcoma, head and neck squamous cell carcinoma, NSCLC, ovarian, bladder, melanoma, gastric, esophageal, breast, colorectal, and other solid tumors)
05
Safety considerations
Potential for on-target, off-tumor toxicity if normal tissues aberrantly express the targetCytokine release syndrome (CRS) and neurotoxicity (class effects of T cell therapies)Risk of immune escape by loss of antigen or HLA downregulationLimited patient eligibility (requires both MAGE-A4 expression and HLA-A*02:01 genotype)
06
Interacting drugs
Afamitresgene autoleucel (afami-cel, marketed as Tecelra)
2 more in the full profile.
07
Biomarkers
Tumor expression of MAGE-A4 by immunohistochemistry (IHC)Patient HLA-A*02:01 genotype (required for presentation and eligibility)B2M and MHC class I expression (for antigen presentation competence)
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