Tumor-associated antigen peptide-MHC class I complex (TAA-pMHC-I) (TAA-pMHC-I)

Tumor-associated antigen (TAA) peptides presented by Major Histocompatibility Complex (MHC) class I molecules are essential targets for modern cancer immunotherapy, representing the primary interface between the intracellular proteome of a tumor cell and the adaptive immune system (Frontiers in Immunology, 2020). These complexes are formed when intracellular proteins—including neoantigens, cancer-testis antigens, or overexpressed self-antigens—are degraded by the proteasome and transported into the endoplasmic reticulum to be loaded onto MHC-I molecules for surface display (Nature Reviews Cancer, 2021). Recognition of these specific peptide-MHC (pMHC) complexes by the T-cell receptor (TCR) of CD8+ T cells triggers cytotoxic activity, leading to the destruction of the malignant cell (Janeway's Immunobiology, 2017). Unlike traditional monoclonal antibodies that target surface proteins, therapies directed at pMHC complexes can target the entire cellular proteome, including previously "undruggable" intracellular oncogenes (Journal of Hematology & Oncology, 2023). Current therapeutic modalities include TCR-engineered T-cell (TCR-T) therapies like afamitresgene autoleucel and bispecific T-cell engagers like tebentafusp, which bridge the pMHC complex with T-cell activation markers (FDA, 2022; FDA, 2024). However, the clinical success of these agents is contingent upon the presence of specific HLA alleles and is often challenged by tumor-mediated HLA downregulation or off-target cross-reactivity with similar peptides in healthy tissues (Immunity, 2022).

Other names

Tumor antigen-HLA complexpMHC-I complexNeoantigen-MHC complexCancer-testis antigen-MHC complexTumor-specific antigen-MHC complexTumor-associated antigen peptides presented by MHC class I on tumor cells

T-cell receptor (TCR) mediated recognition, Bispecific T-cell redirection, TCR-engineered T-cell recognition