MHC class I-presented tumor-associated antigen peptides (MAGE-A1, MAGE-A3, MAGE-A10, CEACAM5, CTAG1B, ERBB2) (TAA-pMHC (MAGE/CEA/NY-ESO-1/HER2))

This target refers to a specific panel of six tumor-associated antigens (TAAs) and cancer-testis antigens (CTAs) that are processed and presented as short peptides on the surface of cancer cells by Major Histocompatibility Complex (MHC) Class I molecules. The panel includes MAGE-A1, MAGE-A3, MAGE-A10, Carcinoembryonic Antigen (CEA/CEACAM5), NY-ESO-1 (CTAG1B), and HER2/neu (ERBB2) [25]. These antigens are highly expressed in various solid tumors, such as melanoma, breast, and lung cancer, while having limited expression in normal tissues, making them attractive targets for immunotherapy [17, 23]. Therapeutic strategies targeting these pMHC complexes include multi-peptide vaccines and T-cell receptor (TCR) engineered T-cell therapies, which aim to prime or redirect CD8+ cytotoxic T lymphocytes to recognize and eliminate tumor cells [1, 18]. A notable challenge in targeting this group is the potential for off-target toxicity due to sequence homology with proteins in healthy tissues, as seen in historical trials where MAGE-A3-specific TCRs cross-reacted with titin in cardiac muscle [4, 22]. Additionally, the efficacy of these therapies depends on the patient's HLA type (most commonly HLA-A*02:01) and the tumor's ability to maintain MHC expression [2, 21].

Other names

6-peptide vaccine targetsCancer-testis antigens (CTAs)Tumor-associated antigens (TAAs)pMHC complexesMAGE-A1/A3/A10, CEA, NY-ESO-1, HER2 peptide-MHC complexes

Recognition of specific peptide-MHC class I complexes by CD8+ T-cell receptors (TCRs) on cytotoxic T lymphocytes, leading to T-cell activation, cytokine secretion (e.g., IFN-gamma), and direct lysis of tumor cells presenting these antigens [2, 22].