Tumor protein p53 (TP53) R248Q mutant peptide presented by HLA-A*11:01 (TP53 R248Q/HLA-A*11:01)

The TP53 R248Q mutant peptide presented by HLA-A*11:01 is a tumor-specific neoantigen complex that serves as a highly specific target for cancer immunotherapy. TP53 is a critical tumor suppressor gene that is mutated in over 50% of human cancers, with the R248Q substitution being one of the most frequent hotspot mutations in the DNA-binding domain (Lo et al., 2020, JCI). This mutation results in the production of a mutant protein that is processed into peptides and presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*11:01. Because this specific peptide-MHC complex is only present on the surface of cancer cells harboring the R248Q mutation and not on healthy cells, it provides a unique window for therapeutic intervention with minimal off-target effects (Hsiue et al., 2021, Science). Current therapeutic approaches under investigation include T-cell receptor-engineered T-cell (TCR-T) therapies and bispecific antibodies designed to recognize the mutant peptide in the context of the HLA molecule (NCT03935828). This target is particularly relevant for patients with solid tumors such as colorectal, pancreatic, and lung cancers who also carry the HLA-A*11:01 allele, which is prevalent in several populations, especially in East Asia. Successful targeting of this neoantigen allows for the selective destruction of malignant cells while sparing normal tissue, addressing a major challenge in precision oncology.

Other names

p53 R248Q/HLA-A*11:01HLA-A*11:01-restricted p53 R248Q neoantigenTP53 R248Q neoepitopep53 R248Q peptide-MHC complex

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