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 stud...

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Veröffentlicht in:European journal of immunology 2008-08, Vol.38 (8), p.2106-2117
Hauptverfasser: Park, Mi-Young, Kim, Hye-Sung, Woo, Sun-Je, Kim, Chang-Hyun, Park, Jung-Sun, Sohn, Hyun-Jung, Kim, Hyung-Jin, Oh, Seong-Taek, Kim, Tai-Gyu
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Sprache:eng
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Zusammenfassung: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-γ-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.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.200737960