Tumor-associated antigen-Major Histocompatibility Complex (TAA-MHC) complex (TAA-MHC)

The Tumor-associated antigen-Major Histocompatibility Complex (TAA-MHC) complex is a critical target in cancer immunotherapy, enabling the immune system to recognize intracellular proteins that are otherwise hidden from surface-binding antibodies (Source: Nature Reviews Drug Discovery, 2021). These complexes consist of short peptide fragments, derived from mutated or overexpressed proteins, which are loaded onto MHC molecules and presented on the tumor cell surface (Source: Janeway's Immunobiology). T-cell receptors (TCRs) on CD8+ or CD4+ T cells specifically recognize these pMHC complexes to initiate a targeted cytotoxic response (Source: Journal of Hematology & Oncology, 2023). Therapeutic strategies such as TCR-engineered T-cell (TCR-T) therapies and TCR-based bispecific engagers (e.g., Tebentafusp) are designed to exploit this mechanism to treat various malignancies (Source: NEJM, 2021). The clinical utility of targeting TAA-MHC is highly dependent on the patient's HLA genotype and the specific expression profile of the target antigen within the tumor (Source: FDA, 2024). Significant safety considerations include the potential for lethal off-target toxicity if the target peptide is shared with healthy tissues, as well as the risk of severe cytokine release syndrome (Source: Frontiers in Immunology, 2022).

Other names

Tumor-associated antigens presented on MHC molecules to T-cell receptorsPeptide-MHC complexpMHCTumor-associated antigen (TAA)Cancer-testis antigen (CTA)Neoantigen-MHC complex

Engineered T-cell receptor (TCR) binding to specific peptide-MHC complexes, leading to T-cell activation and tumor cell lysis (Source: Nature Reviews Clinical Oncology).