Identification and use of T-cell receptors recognizing common tumor mutations

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

We have used HLA transgenic mice to generate multiple TCRs recognizing common human tumor mutations in the context of human MHC presenting molecules. Several of these have no fully human TCRs with the same specificity. Although totally specific for the neoantigen versus the wild type epitope, many of these TCRs are of insufficient affinity to recognize most human tumor lines or organoids. We have screened multiple approaches to enhancing recognition through the introduction of co-receptor and TCR signalling moieties. These studies are continuing, with encouraging results found with a novel IL-12 construct in collaboration with Dr. Peter Kim. These receptors are moving forward with IL-12 to clinical trial.