Efficient antitumor immunity in a murine colorectal cancer model induced by CEA RNA-electroporated B cells.
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.
Park
Mi-Young
MY
Department of Microbiology and Immunology, Kang-Nam St Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Kim
Hye-Sung
HS
Woo
Sun-Je
SJ
Kim
Chang-Hyun
CH
Park
Jung-Sun
JS
Sohn
Hyun-Jung
HJ
Kim
Hyung-Jin
HJ
Oh
Seong-Taek
ST
Kim
Tai-Gyu
TG
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D018274:Electroporation; D005260:Female; D018014:Gene Transfer Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D012313:RNA / Q000378:metabolism*; D014611:Vaccination
D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D012313:RNA