Assistant Professor, Microbiology, Immunology, and Cancer Biology
- BS, Biochemistry, University of St. Thomas
- PhD, Immunology, University of Minnesota
Cancer Biology, Immunology, Microbiology
Engineering cancer-killing T cells to overcome obstacles in solid tumors
Engineering T cells to overcome suppressive signals in the tumor microenvironment
Engineered T cell therapy can effectively kill ovarian cancer cells, but there are still tumor-driven hurdles that T cells must overcome to truly beat ovarian cancer. The goals of the proposed research are to understand precisely how these tumors can block killing by T cells and to develop rational strategies to enhance cancer-killing without causing adverse side effects. Many solid tumors escape T cell therapy using the same obstacles that ovarian cancer employs, so our findings will likely help improve immunotherapies against multiple cancer types.
Engineering T cells to overcome metabolic insufficiency in the tumor microenvironment
A major limitation of adoptive T cell therapy is the progressive loss of cytotoxic T cell efficacy and survival in the tumor. One contributor to reduced efficacy is insufficient metabolic support for T cells in the tumor microenvironment. Many solid tumors have poor vascularization; combined with the increased metabolic demands of tumor cells, this can lead to local nutrient depletion and hypoxia. Notably, limitation of carbon substrates or oxygen can have profound effects on T cell behavior. Since intratumoral T cells are metabolically active and exist in a nutrient-depleted milieu, we posit that T cells may be constrained by this nutrient limitation. We hypothesize that modulating metabolic pathways active in T cells will increase the anti-tumor efficacy of engineered T cells.
Novel pre-clinical models for ovarian cancer research
Dr. Anderson previously collaborated with Dr. Venu Pillarisetty and Dr. Elizabeth Swisher to establish an organotypic slice culture system for ovarian cancer that preserves the viability, morphology and immunosuppressive features of the tumor microenvironment for approximately one week. This cutting-edge pre-clinical model provides a valuable opportunity to evaluate the potential efficacy of new therapies in a heterogeneous immune-competent setting, prior to clinical translation. The slice culture system is an improvement over standard cytotoxicity assays, which utilize two-dimensional monolayers of commercially available or primary tumor cell lines that lack many immunosuppressive structures, proteins, and cytokines in the heterogeneous tumor microenvironment. Collaborative projects aim to evaluate cutting-edge therapeutics and combination therapies, including novel immunotherapies, in this robust pre-clinical model.