Tumor-associated antigen presented by MHC class I (TAA-MHC I)

Tumor-associated antigens (TAAs) presented by MHC class I molecules are critical targets in cancer immunotherapy, representing the primary mechanism by which the immune system identifies malignant cells (1.1.2). These targets consist of short peptide fragments derived from intracellular proteins—such as mutated neoantigens, overexpressed self-proteins, or cancer-testis antigens—that are loaded onto MHC class I molecules and displayed on the cell surface (1.1.3). Recognition of these peptide-MHC (pMHC) complexes by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes triggers a targeted immune response leading to tumor cell lysis (1.1.1). Therapeutic strategies leveraging this target include TCR-engineered T-cell (TCR-T) therapies, cancer vaccines, and bispecific T-cell engagers designed to mimic or enhance TCR specificity (1.2.2, 1.4.1). While highly potent, targeting TAA-MHC complexes faces challenges such as 'on-target, off-tumor' toxicity if the antigen is present on healthy tissues, and the potential for tumor escape through the downregulation of MHC expression (1.1.5). Consequently, patient selection often requires precise HLA typing and confirmation of antigen expression to ensure efficacy and safety (1.2.2).

Other names

Tumor-specific antigenNeoantigenCancer-testis antigenDifferentiation antigenPeptide-MHC class I complexpMHC complexHLA-peptide complex

Drugs targeting these complexes function by redirecting or activating cytotoxic T lymphocytes (CTLs) to recognize and kill tumor cells. This is achieved through T-cell receptor (TCR) binding to the specific peptide-MHC complex, leading to the release of perforins and granzymes, or through the use of bispecific molecules that bridge T cells and tumor cells (1.1.3, 1.2.1).