Scientists at Benaroya Research Institute at Virginia Mason (BRI) have received a $4.5 million, five-year grant from the National Cancer Institute to identify biomarkers that predict the success of checkpoint inhibitor immunotherapy drugs used to treat certain types of cancer. Despite the success of checkpoint inhibitors at improving patient survival, they do not work in all patients and often have serious side effects including sudden-onset symptoms of autoimmune disease.
With the funding, BRI scientists will take a much closer look at how immune response cells --known as T cells -- are affected by checkpoint inhibitor drugs. Ultimately, the scientists hope to identify T cell biomarkers that predict which patients are most at risk for autoimmune effects from checkpoint inhibitors. They will also explore ways to improve the ability of checkpoint inhibitors to kill cancer cells while protecting healthy tissue.
Checkpoint proteins are important regulators of T cells, turning their activity on or off depending on the need for an immune response. Some forms of cancer, in particular solid tumors, protect themselves by sending their own signals to immune checkpoints, suppressing the normal T cell response. As an immunotherapy, checkpoint inhibitors work by taking the "brakes" off the T cells, allowing them to recognize and destroy cancer cells.
Checkpoint inhibitors have played an important role in improving the survival of patients with advanced lung and bladder cancers, as well as melanoma.
"This research will help us predict which cancer patients will benefit most from checkpoint inhibitors, as well as who’s likely to experience autoimmune side effects," said Jane Buckner, MD, President of Benaroya Research Institute. It will also increase understanding of T cells, how they behave in the immune system and what can go awry, she said, so that outcomes can be improved for patients.
Along with Dr. Buckner, the research team includes BRI scientists Peter Linsley, PhD, Erik Wambre, PhD, Laura Chow, MD, of the University of Texas at Austin, Petros Grivas, MD, PhD, of the University of Washington, and John Paul Flores, MD, of Virginia Mason Medical Center.
"Once we better understand why some cancer patients benefit from checkpoint inhibitors, we’ll be positioned to try new approaches for those who haven’t," Wambre explained. "We will determine how this form of immunotherapy impacts the cells of patients, and then learn how we can come up with an improved treatment."
