2017 GRANTEE: Ingunn Stromnes, PhD
University of Minnesota
Research Project: Enhancing Efficacy of Engineered T-cell Therapy for Pancreatic Cancer
Award: 2017 Skip Viragh – Pancreatic Cancer Action Network – AACR Career Development Award
Award Period: July 1, 2017 – June 30, 2019
Dr. Stromnes underwent pre-doctoral training at the National Institutes of Health, followed by a PhD in immunology from the University of Washington. As a postdoctoral scientist at the Fred Hutchinson Cancer Research Center, she developed a novel and promising immunotherapy by genetically engineering T-cells to infiltrate and attack pancreatic cancer without the toxic side effects of chemotherapy. Her postdoctoral studies were conducted under the mentorship of Pancreatic Cancer Action Network research grant recipients Drs. Philip Greenberg and Sunil Hingorani.
Dr. Stromnes is now a faculty member at the University of Minnesota, where she and her lab will continue to push the boundaries of cellular engineering to create safe and effective immunotherapies for pancreatic cancer patients.
To date, a strategy to harness the patient’s immune system to fight off their tumor – known as immunotherapy – has not been clinically successful for most pancreatic cancer patients. T-cells are a critical immune cell type that have the potential to recognize and destroy cancer cells.
However, one of the reasons that T-cell-based therapies haven’t worked in most pancreatic cancer patients is that the tumor cells may not express enough abnormal proteins on their surface to alert and activate T-cells. Also, T-cells are physically repulsed by both the cancer cells and the cells of the stroma, or dense tissue that surrounds the tumors.
To circumvent these challenges, Dr. Stromnes and her research team have developed T-cells with engineered T-cell receptors (TCR) designed to recognize a protein called mesothelin that is expressed on most pancreatic cancer cells. Despite promising early results, the researchers have observed that the TCR-engineered cells become progressively dysfunctional in a genetically engineered mouse model of pancreatic cancer.
For her funded project, Dr. Stromnes aims to decipher the mechanism of these TCR-engineered cells’ dysfunction and determine whether modifications can be made to enhance their activity and ability to target pancreatic cancer cells. Promising strategies will then be evaluated in combination with agents that modulate suppressive cells in the stroma and further developed for clinical testing. The proposed studies are designed to identify translatable strategies to enhance the efficacy of cellular immunotherapies for pancreatic cancer patient treatment.