Cancer cells are good at evading the immune system. By displaying checkpoint proteins on their surface—just as normal cells do—they can signal to the immune system’s T cells that they are to be left alone. Certain immunotherapies target these checkpoint proteins or the corresponding proteins on T cells to help the immune system recognize and kill cancer cells. However, not all patients benefit from this type of treatment.
Dr. Ravi Patel, a Bentson Translational Research Fellow in the Department of Human Oncology, is hoping to improve the effectiveness of immune checkpoint blockade for more patients by researching ways to combine these agents with radiation, which may enhance the immune response. He recently received an American Society of Clinical Oncology (ASCO) Young Investigator Award, which includes a one-year, $50,000 grant to support this work.
The award will help him build on preclinical studies he has conducted with Drs. Zachary Morris, assistant professor of human oncology; Paul Sondel, professor of human oncology and pediatrics; and Jamey Weichert, associate professor of radiology. By treating mice with a novel form of molecular targeted radiation therapy—a systemic radiation injection preferentially taken up by tumors—followed by an immune checkpoint inhibitor (anti-CTLA-4 and/or anti-PD-1), the research team has achieved a cure rate of approximately 50 percent. This is an impressive result because the tumor cell lines they are targeting were selected specifically because they do not respond to either the checkpoint inhibitors or the radiation alone.
The dose of radiation used in this treatment strategy is less than what is typically used clinically. The intent is not to kill the cancer cells with radiation but rather to stress them in a way that makes them more easily recognized by the immune system. This molecular targeted radiation does not appear to affect immune cells in blood, but preliminary data show that it can reduce suppressive immune cells in tumors and stimulate recognition of the tumor by the immune system.
This initial study found the approach to be effective in mice with one or two tumors. Patel will use the grant to study its effectiveness in treating preclinical models of metastatic cancer and expand this research to include other checkpoint inhibitors and other types of cancer. He hopes to have enough data in a year to be able to advance this line of research to a clinical trial.
Patel, who has an MD and a PhD in biomedical engineering, joined the department in July 2017. His eventual goal is to obtain an independent research position as a physician-scientist, where he will see cancer patients and direct their treatment and run his own research lab aimed at discovering new cancer treatments.
“I’m grateful to ASCO for this award,” Patel says. “Awards like this not only help me build my career as a physician-scientist, but more importantly, they enable me to pursue research that has the potential help more patients.”
Morris adds: “Ravi is an absolutely outstanding clinician-scientist with an incredible dedication and passion for cancer research. I was so pleased to learn that he had been selected for this ASCO Young Investigator Award, not only because of the support that this grant will provide for his innovative research, but even more so because of the career enhancement that this award provides to this rising star in the emerging field of immuno-radiation oncology.”