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The MAGE-A3 peptide presented by HLA-A*01 is a cancer-specific antigenic peptide (EVDPIGHLY 168–176) from the melanoma-associated antigen family MAGE-A3, displayed by the MHC class I molecule HLA-A*01 on the surface of tumor cells. Recognition of this complex by engineered T cells forms the basis for certain adoptive cancer immunotherapies. While MAGE-A3 is normally silent in adult tissues except testes, its frequent re-expression in diverse cancers makes it an attractive immunotherapeutic target. However, engineered TCRs targeting this complex have exhibited unintended cross-reactivity with similar peptides (e.g., Titin), leading to severe safety concerns, most notably fatal cardiac toxicity in clinical settings, highlighting the importance of precise specificity in therapeutic design[1][5].
Recognition and killing of MAGE-A3-expressing tumor cells by engineered T cells (includes cytotoxicity and cytokine release)\nEngagement of peptide–MHC complex by therapeutic TCRs leading to immune activation
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