David Schlaepfer, PhD

One of the biggest challenges to extending patient survival from recurrent ovarian cancer is to understand how these tumors can “hide” from detection by cells of the immune system. Immunotherapy involves treatments that use the body’s own immune system to help fight cancer. Despite successes in other cancer types, immunotherapy treatments for ovarian tumors have had limited success in promoting patient survival. Our work builds upon the idea that ovarian tumors upregulate immune “protective” molecules and that these provide a “shield” against immune cell attack. We have found that the activity of a protein (FAK) within ovarian tumor cells drives protection signals and that the combination of chemotherapy blocking FAK (weakening the shield) with immunotherapy resulted in tumor shrinkage. Mouse survival was associated with the gathering of immune cells within and nearby tumor sites in the process of tumor killing. In mice, we have also identified measurable markers that circulate in blood, the presence of which increased as tumors were being attacked by immune cells. In this proposal, we will treat mice with a novel combination of tumor- and immune-targeting therapies and will validate the timing and extent of marker changes in tissues and blood as the tumor shrinks. A clinical trial to test this novel treatment combination and marker evaluation is proposed. The benefit of measuring markers in blood is that this does not involve surgery and that this may provide the clinician with early insights of patient response.