Efficient antitumor immunity in a murine colorectal cancer model induced by CEA RNA-electroporated B cells.

Abstract

RNA electroporation as a gene delivery method is more feasible and safer as compared with viral vectors. RNA-loaded dendritic cells (DC) have been used to induce T cell responses against tumor rejection antigens and B cells can also act as antigen-presenting cells for cellular vaccines. In this study, we compared B cells and DC, after electroporation with carcinoembryonic antigen (CEA) RNA, for their capacity to generate cytotoxic T lymphocytes and antitumor immunity. Vaccination using these B cells induced levels of IFN-gamma-secreting T cells and cytotoxic T cells comparable to those induced by DC. Intravenous administration was the optimum route for the B cell vaccine, while subcutaneous administration was the optimum route for the DC vaccine. The B cell vaccine predominantly generated CEA-specific CD4(+) T cells, whereas the DC vaccine generated CD8(+) T cells. Moreover, the B cell vaccine induced higher levels of anti-CEA antibodies than the DC vaccine. A heterogeneous prime-boost using B cells and DC failed to show any synergistic effects; however, the B cell vaccine did inhibit tumor growth and prolonged survival to a similar extent as the DC vaccine. Such RNA-electroporated B cells may prove useful as cellular tumor vaccines with potential clinical application.