p53 peptide-MHC complex (p53 pMHC)

p53-derived peptide epitopes presented on MHC molecules are critical targets for cancer immunotherapy, representing either neoantigens derived from somatic mutations or overexpressed wild-type peptides [6, 13]. The p53 protein, a master tumor suppressor, is frequently mutated in a wide array of human cancers, leading to its stabilization and subsequent presentation as peptide fragments on the cell surface via Major Histocompatibility Complex (MHC) Class I molecules [10, 14]. These peptide-MHC (pMHC) complexes serve as specific ligands for T-cell receptors (TCRs), allowing the immune system to distinguish malignant cells from healthy tissue [5, 19]. Therapeutic interventions, such as TCR-engineered T-cell (TCR-T) therapies (e.g., NT-175), bispecific T-cell engagers, and cancer vaccines, aim to exploit this recognition to induce T-cell mediated destruction of tumor cells [1, 2, 7]. However, challenges such as low epitope density on the cell surface and the risk of off-target cross-reactivity with wild-type p53 peptides in normal tissues necessitate high specificity in drug design [5, 14]. Additionally, tumors may evade detection through mechanisms like MHC downregulation or altered antigen processing by enzymes like ERAP1 [9, 18].

Other names

p53 peptide-MHC complexp53 neoantigen-MHC complexp53-derived peptide-HLA complexp53 neoepitopep53-MHC complexp53-derived peptide epitopes presented on MHC molecules

T-cell mediated cytotoxicity, T-cell redirection, and immune activation through TCR-pMHC recognition