BET Proteins and T-Cell Function: Joseph A. Fraietta, PhD

“What we showed was that through the use of this well-characterized and potent selective small molecule, JQ1, the bromodomain and extra terminal domain that JQ1 blocks really plays a fundamental role in this down-regulation of vector-driven CAR transgene transcriptional activity.”

Investigators from the University of Pennsylvania’s Perelman School of Medicine have found that small-molecule inhibitors, such as JQ1, which is currently used to treat a variety of cancers, can “reinvigorate” patient T cells and improve chimeric antigen receptor (CAR) T-cell function. This research may address the problem of exhausted T cells in CAR T-cell therapy.

Joseph A. Fraietta, PhD, assistant professor, microbiology, and director, Solid Tumor Immunotherapy Lab, Center for Advanced Cellular Therapies, University of Pennsylvania, and colleagues found that JQ1 inhibits the bromodomain and extra terminal (BET) proteins, which otherwise disrupt CAR expression and T cell histone function in chronic lymphocytic leukemia (CLL).

GeneTherapyLive spoke with Fraietta to learn more about the mechanism of small-molecule inhibitors and how they affect T-cell function. He also discussed his findings on the mechanism of T-cell exhaustion.

REFERENCE

Existing drug may help improve responses to cellular therapies in advanced leukemias. News release. University of Pennsylvania. August 16, 2021. https://www.pennmedicine.org/news/news-releases/2021/august/existing-drug-may-help-improve-responses-to-cellular-therapies-in-advanced-leukemias