Dendritic cell-tumor cell hybrids enhance the induction of cytotoxic T lymphocytes against murine colon cancer: a comparative analysis of antigen loading methods for the vaccination of immunotherapeutic dendritic cells.
Dendritic cells (DCs) have been used successfully for inducing effective anti-tumor immune responses in advanced cancer patients undergoing tumor-specific immunotherapy. Appropriate antigen pulsing is a crucial parameter for optimizing the efficacy of immunotherapy as well as anti-tumor protection therapy. Using a murine colon cancer model, we evaluated the anti-tumor efficacy of four different preparations of DC vaccines that contained either a whole tumor or its derivatives, including i) DCs pulsed with tumor lysate, ii) DCs pulsed with necrotic tumor cells, iii) DCs pulsed with apoptotic tumor cells, and iv) DC-tumor cell fusion hybrids. Our data show that DC-tumor cell fusion hybrids and DCs pulsed with irradiated apoptotic tumor cells were more potent than DCs with freeze-thawed necrotic tumor cells for the induction of protective anti-tumor responses. The vaccination of DCs pulsed with tumor lysate failed to elicit any anti-tumor effect. In animals administered with higher doses of a tumor-cell challenge, DC-tumor cell fusion hybrids elicited the most effective anti-tumor response. Among the preparations tested, mice immunized with DC-tumor cell fusion hybrids resulted in the greatest induction of cytotoxicity as measured by the cytotoxic T lymphocyte activity of both the splenocytes and the Thy1.2-positive T lymphocytes. Furthermore, the in vitro production of IFN-gamma polarized to the Th1 cytokine responses was highest in the splenocytes derived from mice vaccinated with DC-tumor cell fusion hybrids. Our results suggest that DC-tumor cell fusion hybrids are more potent inducers of protection against solid tumors, such as colon cancer, than other antigen-loading strategies using whole tumor cell materials.
Yasuda
Takashi
T
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kobe University, Kobe 650-0017, Japan.
Kamigaki
Takashi
T
Nakamura
Tetsu
T
Imanishi
Tatsuya
T
Hayashi
Shun
S
Kawasaki
Kentaro
K
Takase
Shiro
S
Ajiki
Tetsuo
T
Kuroda
Yoshikazu
Y
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D017209:Apoptosis / Q000502:physiology; D019496:Cancer Vaccines / Q000276:immunology*; D002457:Cell Extracts / Q000276:immunology; D002459:Cell Fusion; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006822:Hybrid Cells; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis / Q000503:physiopathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D002457:Cell Extracts