Identification of small molecules enhancers of adoptive T cell therapy efficacy

National Center For Advancing Translational Sciences

Investigators

Abstract

Adoptive cell therapies targeting somatic mutations arising in cancer cells can lead to durable clinical responses. However, cancer cells can evade immune cell killing via a number of different mechanisms. One way is to epigenetically downregulate the expression of antigens or major histocompatibility complexes (MHC) responsible for presenting given antigens for T cells. The goal of this project is to identify a class of drugs that can enhance T cell-induced tumor cell killing. During this period, the project team has developed a 384-well high-throughput amenable assay and screened the NCATS Pharmaceutical Collection and Epigenetics library. A number of hits clustered into specific mechanistic classes were identified and validated, and are currently undergoing more detailed characterization to fully understand their modes of action.