Identification of novel KRAS^G12D neoantigen specific TCRs and a strategy to eliminate off-target recognition.

ABSTRACT:

Background

T cell receptor (TCR)-engineered T cells targeting neoantigens originated from mutations in KRAS gene have demonstrated promising outcomes in clinical trials against solid tumors. However, the challenge lies in developing tumor-specific TCRs that avoid cross-reactivity with self-antigens to minimize the possibility of severe clinical toxicities. Current research efforts have been put towards strategies to eliminate TCR off-target recognition.

Methods

Naive T cell repertoire was used for screening KRAS^G12D-reactive TCRs. Specific TCRs were subsequently identified and their functionality was assessed using TCR Jurkat cells and TCR T cells. Peptide specificity was evaluated using the X-scan assay. To enhance TCR specificity for KRAS^G12D and redu

SUBMITTER: Han X 

PROVIDER: S-EPMC11740425 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature