T-cell receptor specific for p53-derived peptides (p53-specific TCR)

The T-cell receptor (TCR) on p53-specific CD8+ and CD4+ T cells is a specialized protein complex that recognizes peptides derived from the p53 tumor suppressor protein when presented by Major Histocompatibility Complex (MHC) molecules (Lo et al., Science, 2019). In many cancers, p53 undergoes hotspot mutations, such as R175H or R248W, which create unique neoantigens that are not present in healthy cells (Deniger et al., JCI, 2018). These TCRs are the primary components used in adoptive T-cell receptor (TCR-T) therapies, where a patient's own T cells are genetically modified to express a TCR that specifically targets these p53 mutations (NCT03431311). Upon binding to the p53 peptide-MHC complex, the TCR triggers a signaling cascade that activates the T cell to destroy the tumor cell through the release of cytotoxic factors like perforin and granzymes (Malekzadeh et al., JCI, 2019). This therapeutic approach is designed to treat a variety of solid tumors, including ovarian, colorectal, and pancreatic cancers, by leveraging the high specificity of the immune system. However, a major challenge remains the potential for off-target toxicity if the TCR cross-reacts with wild-type p53 or other similar proteins in normal tissues. Monitoring for cytokine release syndrome and ensuring strict HLA-restriction are essential safety protocols in clinical applications of these TCRs.

Other names

p53-reactive T-cell receptorp53-TCRanti-p53 TCRp53-specific TCRT-cell receptor specific for p53-derived peptides

Recognition of p53-derived peptides (neoantigens) presented by specific HLA molecules on tumor cells, triggering T-cell mediated cytotoxicity.