“Juicing” T Cells with Small Molecules Enhances Immune Response Against Melanoma

"Juicing" Th17 cells with FDA-approved small molecule β-catenin and p110δ inhibitors during in vitro expansion for adoptive T cell therapy (ACT) profoundly improves their therapeutic properties, report investigators at the Medical University of South Carolina (MUSC) in an article published online on April 20, 2017 in JCI Insight. The open-access article is titled “β-Catenin and PI3Kδ Inhibition Expands Precursor Th17 Cells with Heightened Stemness and Antitumor Activity.” ACT involves harvesting T cells, rapidly amplifying and/or modifying them in the laboratory to boost their cancer-fighting ability, and then reinfusing them back to the patient to boost anticancer immunity. One challenge for ACT has been that the rapid expansion of T cells in the laboratory can cause them to age and wear out, decreasing their longevity after reinfusion. "Juicing" Th17 cells with the FDA-approved small molecules enhanced their potency, function, and stem-like (less differentiated) quality, suggesting that they would persist better after reinfusion into patients, and also reduced regulatory T cells in the tumor microenvironment, which can blunt the immune response. These findings highlight novel investigative avenues for next-generation immunotherapies, including vaccines, checkpoint modulators, and ACT. "This is exciting because we might be able to overcome some of the delays and disadvantages of rapid expansion in the laboratory," explains senior author Chrystal M. Paulos (photo), PhD, Associate Professor of Immunology and Endowed Peng Chair of Dermatology at MUSC and a member of the MUSC Hollings Cancer Center.