Tumor protein p53 R248Q neoantigen (TP53 R248Q)

The TP53 R248Q neoantigen is a tumor-specific peptide derived from a common missense mutation in the TP53 gene, which encodes the tumor protein p53. This specific mutation involves an arginine-to-glutamine substitution at residue 248, a hotspot location within the DNA-binding domain that frequently occurs in various malignancies, including colorectal, lung, and pancreatic cancers (PMID: 28825020). As a neoantigen, the mutated peptide is processed by the proteasome and presented on the cell surface by specific Human Leukocyte Antigen (HLA) molecules, most notably HLA-A*11:01 (PMID: 29907661). This presentation allows the immune system to distinguish malignant cells from healthy tissue, making it an ideal target for precision immunotherapies such as T-cell receptor (TCR) engineered T-cell therapy and neoantigen-based vaccines. While the mutation itself leads to a loss of p53's tumor-suppressive functions—such as cell cycle arrest and apoptosis induction—the resulting neoantigen provides a unique flag for therapeutic intervention. Current clinical efforts focus on developing TCR-T therapies that can specifically recognize the R248Q peptide-HLA complex to induce targeted tumor cell lysis (NCT03937791). Challenges in targeting this neoantigen include the requirement for specific HLA matching and the potential for tumor escape through HLA downregulation or antigen loss.

Other names

p53 R248QMutant p53 R248QTP53 Arg248Glnp53-R248Q neoepitope

T-cell receptor (TCR) mediated recognition of the peptide-HLA complex leading to T-cell activation and tumor cell lysis.