Event
BIOE Seminar: Overcoming immune suppression in solid tumors to enhance the efficacy of engineered T
Friday, April 25, 2025
9:00 a.m.-10:00 a.m.
A. James Clark Hall, Room #2121
Alex Xu
alexmxu@umd.edu
Kristin Anderson
Assistant Professor
University of Virginia
Overcoming immune suppression in solid tumors to enhance the efficacy of engineered T cell therapy
Abstract
The 5-year survival rate for ovarian cancer patients remains below 50%, underscoring the need for innovative therapies. One promising approach involves engineering T cells to target proteins uniquely overexpressed in tumors, thereby controlling tumor growth without toxicity to healthy tissues. Mesothelin (Msln) contributes to the invasive phenotype in ovarian cancer and has limited expression in healthy cells, making it a candidate immunotherapy target. Our previous results in an ovarian cancer mouse model demonstrated that T cells engineered to express a T cell receptor targeting Msln (TCRMsln) mediated therapeutic activity, delaying tumor growth and prolonging mouse survival. However, suppressive features in the tumor microenvironment significantly reduced engineered T cell persistence and function. We leveraged synthetic fusion proteins and checkpoint blockade to rationally disrupt known suppressive pathways, which led to significantly enhanced therapeutic T cell persistence, function and antitumor efficacy. Many solid tumors share the same immune-suppressive obstacles, suggesting these approaches may offer opportunities to enhance immunotherapy efficacy in a variety of malignancies.
Speaker Bio
Dr. Kristin G. Anderson is an Assistant Professor in the Departments of Microbiology, Immunology and Cancer Biology and Obstetrics and Gynecology at the University of Virginia (UVA) in Charlottesville, VA. She is also a member of the Beirne B. Carter Center for Immunology Research and the UVA Comprehensive Cancer Center Cancer Therapeutics Program.
Dr. Anderson received her Ph.D. in Immunology from the University of Minnesota, where she studied immune responses to lung infection and developed a method that is now widely used in the field to discriminate between immune cells in the blood from those in the tissue. During her postdoctoral training at the Fred Hutchinson Cancer Center and University of Washington, she pivoted her research focus to engineered T cell immunotherapy, leveraging cutting-edge genetic engineering strategies to enhance the immune system to kill ovarian and pancreatic cancer. Her current research program interrogates novel genetic engineering approaches to overcome immune-suppression in solid tumors, with the ultimate goal of translating her findings into treatments for patients. Her team uses patient samples to identify obstacles in the solid tumor microenvironment that dampen T cell persistence and function, and then they evaluate strategies that improve the function of genetically engineered anti-tumor T cells in pre-clinical models that recapitulate features of the human tumor microenvironment.
