p53-specific T-cell receptor (p53-TCR) (p53-TCR)

p53-specific T-cell receptors (p53-TCRs) are specialized immune receptors engineered or isolated to recognize peptide fragments of the p53 tumor suppressor protein presented by Major Histocompatibility Complex (MHC) molecules (Lo et al., Science, 2019). Because TP53 is the most frequently mutated gene in human cancers, these TCRs often target specific "hotspot" mutations, such as R175H or R248W, which function as neoantigens unique to the tumor (Malekzadeh et al., Cancer Discovery, 2019). In adoptive cell therapy, patient-derived T-cells are genetically modified to express these TCRs, allowing them to identify and eliminate cancer cells that display the p53-MHC complex on their surface (Hsiue et al., Science, 2021). This approach is being investigated for a variety of solid tumors, including ovarian, colorectal, and lung cancers, where p53 mutations are prevalent (NCI, 2023). The primary therapeutic challenge involves ensuring high specificity for the mutant peptide to avoid "on-target, off-tumor" toxicity against healthy cells expressing wild-type p53 (Hsiue et al., Science, 2021). By leveraging the precision of the TCR-MHC interaction, this modality represents a potent strategy for personalized cancer immunotherapy.

Other names

TP53-specific TCRp53-reactive T-cell receptorp53-targeting TCRp53-MHC-specific TCR

Recognition of p53-derived peptides (mutant or wild-type) presented by MHC class I molecules, triggering T-cell activation and targeted lysis of tumor cells.