CAR-T Cell Therapy May Be Effective Against Solid Tumors

Boosting immune system T cells to effectively attack solid tumors—such as breast cancers—can be done by adding a small molecule to a treatment procedure called chimeric antigen receptor-T (CAR-T) cell therapy, according to a study by researchers at the UNC Lineberger Comprehensive Cancer Center. The findings were published in the Journal of Experimental Medicine.

"We know that CAR-T cells are safe for patients with solid tumors but so far they have not been able to cause significant tumor regression in the overwhelming majority of people treated," said study leader Jonathan S. Serody. "Now we may have a new approach to make CAR-T cells work in solid tumors, which we think could be a game-changer for therapies aimed at an appreciable number of cancers."

Serody and colleagues looked for ways to direct the lab-expanded cells toward the site of solid tumors. They focused on Th17 and Tc17 cells, which are known to have longer persistence in the micro-environment that surrounds a tumor, in part due to their better survival capabilities. To boost accumulation of Th17 and Tc17 cells near solid tumors, they turned to two small molecules that can activate an immune response: the stimulator of interferon genes (STING) agonists DMXAA and cGAMP.

In their experiments, mice injected with cGAMP exhibited enhanced proliferation of T cells and those cells migrated to the tumor site. The end result was a significant decrease in tumor growth and enhanced survival.

"We hope to be able to study cGAMP in humans fairly soon," concluded Serody. "We will look to see if we can produce improvements in the treatment of head and neck cancers first, and if that proves promising, move into other forms of cancer by using CAR T cells generated by one of our colleagues here at UNC."