André Lieber, MD, PhD
University of Washington
2016 Lester and Bernice Smith Challenge Award Grant
Immuno-Prophylaxis of Ovarian Cancer Associated with High-Risk Germ Line Mutations
Dr. Lieber’s project proposes a prophylactic gene therapy approach to introduce genes encoding antibodies into hematopoietic stem cells from the bone marrow. Ovarian cancer cells normally produce signals that inhibit immune cells from attacking and thereby evade destruction by the immune system. Ovarian cancer cells also attract hematopoietic stem cells from the bone marrow which will mature into peripheral blood cells and aid in the growth and metastasis of the cancer cells. The approach of Dr. Lieber’s project is to modify hematopoietic stem cells with genes encoding antibodies against PD-L1 and CTLA4, which are both molecules that inhibit immune system function. If the modified stem cells are ever called upon by ovarian cancer cells, instead of helping the cancer cells to growth, the modified stem cells will produce antibodies that will remove the inhibition of the immune system. The immune system will then be able to function properly and destroy the ovarian cancer cells. This project will demonstrate whether this approach will prevent the development of spontaneous cancer in cancer-prone mouse models of ovarian and breast cancer. Successful results in this study could translate into a future clinical trial available to women at high risk for ovarian and breast cancer. Successful results could also translated to ovarian cancer patients to prevent or delay ovarian and breast cancer reccurrence after standard treatment and may be relevant for treating other types of cancer.