Targeting FRβ+ tumor associated macrophages with car T cells in ovarian cancer

Background Chimeric antigen receptor (CAR) T cell therapy has shown dramatic clinical success in CD19+ leukemia and lymphoma patients. However, CAR T cell therapy for epithelial cancers has been less successful. Developing effective CAR T cell therapies for other types of cancer may involve overcoming several obstacles associated with solid tumors. Poor blood supply and dense stromal components can hinder access of CAR T cells to tumor cells. In addition, immunosuppressive elements in the tumor microenvironment may suppress T cell functional activity. Tumor associated macrophages (TAMs) have been identified as key pro-tumor players in the microenvironment. Tumors co-opt macrophage function to help promote tumor growth (“M2” polarization) via many diverse mechanisms including promoting angiogenesis, metastasis, and immune evasion. Indeed, the presence of TAMs correlates with worse overall prognosis in many types of cancer, including ovarian cancer patients. We hypothesized that utilizing the power of CAR T cells to target TAMs could be an effective way to improve CAR T cell therapy in epithelial cancer.