Engineered ovarian cancer artificial antigen presenting cells (aAPCs) support CD8+T cells growth and function

Abstract

Ovarian cancer is one of the leading causes of cancer death in women. Immunotherapy may play a potential role as an ovarian cancer treatment. In this study, we demonstrated that the ovarian cancer cell line OV79m can be engineered to function as an aAPC, by using lentiviral vectors to introduce the costimulatory molecules CD64, CD86 and 41BBL (OV79m-aAPCs). The OV79m-aAPCs support long-term polyclonal expansion of human CD8+ T cells from normal donors in vitro, and the cell expansion does not require exogenous cytokines. Flow cytometric analysis has shown that (1) polyclonal expanded CD8+ T cells from normal donors have an early effectors’ CD8+ T cell phenotype, (2) the expanded CD8+ T cells produce the cytokines IL-2 and IFNγ, (3) CD107a expression can be detected on the cell surface of CD8+ T cells following activation. Further studies have shown that OV79m-aAPCs transduced to express influenza matrix protein support long term expansion of Flu-specific CD8+ T cells from normal donors. The expanded Flu-specific CD8+T cells produce IFNγ and are CD107a positive. In conclusion, our data suggest that ovarian cancer cell lines can be engineered as effective APCs; therefore they have therapeutic potential for ovarian cancer patients. Future studies need to examine if the OV79m-aAPCs can expand tumor-specific T cells from patient tumor infiltrating T cells (TILs), and if the expanded TILs are functional in vivo.