“Immunotherapy holds the key for curing cancer,” says Zihai Li, MD, PhD, adding that the Pelotonia Institute for Immuno-Oncology (PIIO) is helping to lead the way. Li is the founding director of the PIIO, which was created in 2019 with the help of a five-year, $102.3 million funding commitment from Pelotonia, the annual bike ride that has raised $218 million for cancer research. On Episode 75 of the James Cancer-Free World podcast, Li provided a detailed update on some of the exciting work being done by the PIIO’s world-class scientists. Listen via the video player above or on Soundcloud. Recruiting “Since we started in July 2019, we have recruited 15 new investigators — world-class scientists,” Li says. “We are an army of people, and you need that to advance this work.” Cell therapy program This is the basic science component of the PIIO — understanding cancer cells and the cells in the body’s immune system that fight them, such as T cells and the aptly named natural killer cells. “The technology is there to expand and train those cells and infuse them back into patients, and we have a very robust program for doing so,” Li explains. Cancer scientists have identified PD-1, a protein found on cancer cells that enables them to hide from the body’s immune system. “We have discovered ways to turn that off and have the body’s immune system recognize and attack cancer cells,” Li says, adding that approximately 20 percent of cancer patients have the PD-1 mutation and respond well to immunotherapy treatment. Fighting GARP “In my lab, we are looking at GARP,” Li says of glycoprotein-A repetitions predominant, a molecule that, much like PD-1, hides cancer cells from the immune system. Through research and pre-clinical trials, Li and his lab have been able to “block GARP and make the tumor visible to the immune system.” The next step is a clinical trial. Li says that it’s not yet known how many cancer patients have the GARP mutation, but it could be a sizable percentage of those patients who do not respond to chemotherapy treatment that targets PD-1. “Even for those 20 percent who do respond, we think adding this treatment [to attack GARP] will make it even more effective.” The Hedgehog molecule Yiping Yang, MD, PhD, the director of The James Division of Hematology, and his lab are investigating a genetic mutation with a shape that resembles a hedgehog. This mutation disrupts the signaling ability of the body’s immune system, allowing cancer cells to avoid detection. “Dr. Yang is working with [James physicians] David Carbone, MD, PhD, and Dwight Owen, MD, MS, on a clinical trial that will combine a hedgehog inhibitor with a PD-1 inhibitor,” Li says, adding that this treatment could be applied to several different types of cancer. Looking ahead The passion and determination of Li come through quite clearly. “We think cancer medicine is reaching a critical point,” he says. “This requires everyone to work together to tackle this disease in a fundamentally different way. We know immunotherapy holds the key for cancer cures. We’re not there yet for every patient and every cancer, so we have a lot of work to do.”