T cell therapy targeting a public neoantigen in microsatellite instable colon cancer reduces in vivo tumor growth.

ABSTRACT: T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance. The transforming growth factor β Receptor II frameshift mutation (TGFβRII^mut) is found in Lynch syndrome cancer patients and

SUBMITTER: Inderberg EM 

PROVIDER: S-EPMC5414866 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature