In this project, we want to specifically boost antitumor immune responses. Immune “T” cells can selectively kill abnormal cells, and some of a patient’s own T cells may be able to recognize and kill cancer cells naturally. But, this response is usually not sufficient to control ovarian cancer. We propose developing ways to genetically engineer large numbers of T cells that could better target a patient’s tumor when used as therapy. T cell therapy has already shown great success against one type of leukemia, and clinical trials have begun to evaluate T cell therapies against solid tumors, such as lung cancer. Our lab has developed novel ways to identify molecules on T cells (called T cell receptors, or TCRs) that bind specific molecules on tumor cells and activate T cells to kill those cancers. We can efficiently engineer T cells to target the cancer-associated proteins known as Wilms’ Tumor Protein 1 (WT1) and mesothelin (Msln).
It is well-known that many tumors obtain and use energy differently than normal cells, and this abnormal metabolism can support tumor growth. Moreover, certain tumor-associated metabolic features can apparently prevent T cells from efficiently killing tumors. For example, ovarian tumor cells depend on abnormal levels of glucose to support their growth; they therefore increase expression of glucose-importing proteins, which deplete glucose from the area around the tumor. As T cells also require high levels of glucose, and tumor cells can out-compete T cells for these nutrients, T cells cannot function and often die as they enter the tumor environment. This project aims to better understand the metabolic mechanisms by which ovarian tumors evade T cell killing, and to develop strategies to invigorate antitumor T cells in the nutrient-poor tumor environment.
This grant was made possible in part by generous donations from OCRA Community Partners, including the Amy Krouse Rosenthal Foundation, Tell Every Amazing Lady About Ovarian Cancer, and the Janice Lopez Ovarian Cancer Foundation.
Dr. Kristin G. Anderson is currently a postdoctoral research fellow at the Fred Hutchinson Cancer Research Center and the University of Washington in Seattle, WA in the lab of Dr. Philip D. Greenberg. Dr. Anderson received her B.S. from the University of St. Thomas and her Ph.D. in Immunology from the University of Minnesota, where she studied T cell responses to lung infection and developed a method that is now widely used in the field to discriminate and isolate intravascular from tissue leukocytes. During her graduate work, she was diagnosed with and underwent treatment for localized breast cancer.
Her experience as a patient inspired her to apply her immunology training to the field of cancer biology and translational immunotherapy. Her current research focuses on developing molecular engineering strategies to improve T cell killing in ovarian cancer, with the ultimate goal of translating her findings into treatment protocols for patients. She leads a team that uses patient samples to identify immunosuppressive features in the tumor microenvironment, then uses mouse models of cancer that recapitulate these features to evaluate strategies that improve the migration, persistence, and function of genetically engineered anti-tumor T cells.
Dr. Anderson received several awards for her graduate work, including the University of Minnesota Medical Foundation’s Bacaner Research Award and the President’s Student Leadership and Service Award. For her post-doctoral work, she has been awarded an American Association for Cancer Research (AACR) Women In Cancer Research Award, an AACR Scholar-In-Training Award, a Keystone Symposia Future of Science Fund Scholarship, two American Association of Immunologists (AAI) Travel Awards, and a Society for Immunotherapy of Cancer (SITC) Presidential Travel Award. She has been awarded a T32 postdoctoral fellowship, as well as funding support from the Fred Hutch Solid Tumor Translational Research Program, Colleen’s Dream Foundation, the Brotman Baty Single Cell Initiative, the Fred Hutch Holiday Gala Challenge Grant, and other anonymous philanthropic donations.