T-cell immunotherapy is a revolutionary treatment that harnesses a patient’s own immune cells to kill cancer. A Wilmot Cancer Institute scientist received a $2.8 million award to investigate the serious and sometime fatal side effects associated with the cutting-edge therapy and to develop an improved version.
Preliminary data from Principal Investigator Minsoo Kim, Ph.D., shows that the problem with T-cell immunotherapy may lie in the migration patterns of T-cells as they hunt down cancer.
T-cells are a type of white blood cell that fights infection; for cancer, they can be engineered and reprogrammed as a “living drug.” This approach is broadly known as “adoptive cell transfer” and the type of therapy that has advanced the furthest is called CAR T-cell treatment.
The treatment works like this: T-cells are extracted from a cancer patient, and then scientists alter them outside the body with bioengineering techniques to target receptors on cancer cells. Once they’re injected back into the patient, the T-cells are supposed to migrate toward the cancer. But this is when problems can arise: Before reaching their targets, the T-cells often hide in non-cancerous tissues including the lungs, for several days. While sequestered, they rev up the body’s natural immune system to an extreme and inadvertently damage vital organs.
“This is already a very promising treatment but if we can better understand the homing properties of the cells, and steer them more quickly and directly toward the cancer, we may be able to minimize side effects and make the treatment more effective,” said Kim, a Dean’s professor of infectious diseases and of Pharmacology and Physiology. He is also co-leader of Wilmot’s Cancer Microenvironment Research Program.
Kim’s early data describes the molecular transformations that take place during this period of T-cell sequestration — with the aim of finding new ways to control the T-cell migration more effectively and with less toxicity. One of Kim’s special interests is in optics, and previous research by his laboratory has focused on using LED chips to stimulate the movement of T-cells toward the bull’s-eye, cancer.
Wilmot has been at the forefront of this type of immunotherapy since 2016, when it was selected as one of several national sites to carry out a clinical trial evaluating CAR T-cell therapy in lymphoma patients. A year later, the U.S. Food and Drug Administration approved a CAR T-cell treatment called Yescarta, developed by Kite Pharma, and Wilmot again was among the first sites in the world to offer it to qualifying cancer patients.
The National Institutes of Health is funding the project through 2024. Richard Waugh, Ph.D., professor of Biomedical Engineering and Vice Provost for Research at the University of Rochester, is the co-Principal Investigator with Kim on the project. Patrick Reagan, M.D., who specializes in treating patients at Wilmot with CAR T-cell therapy, is a co-investigator.