T cell receptor-engineered T cells targeting the TP53R248Q neoantigen elicit antitumor effects in human cancer models.

ABSTRACT: Malignant tumors with TP53 mutations exhibit poor therapeutic outcomes and high recurrence rates. T cell receptor (TCR)-based T cell therapy shows great promise for targeting intracellular cancer neoantigens. However, the immunogenic potential of TP53 hotspot mutations remain poorly characterized. Here, we identify a immunogenic neoantigen derived from the recurrent TP53R248Q mutation, presented by the prevalent Human Leukocyte Antigen (HLA)-A*11:01 allele. Additionally, we isolated a TP53R248Q reactive TCR that specifically recognize the TP53R248Q mutation without any discernable cross-activity to cognate wild-type TP53 or other TP53 mutants at the same codon position. Functional characterization revealed that TP53R248Q TCR-T cells exhibited selectively cytotoxicity against tumor cells ex

SUBMITTER: Shen L 

PROVIDER: S-EPMC12948421 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature