2019 Mentored Investigator Grant Recipient — Kristin G. Anderson, PhD
Project Summary
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.