PMID- 17089056 OWN - NLM STAT- MEDLINE DCOM- 20061228 LR - 20061107 IS - 1021-335X (Print) IS - 1021-335X (Linking) VI - 16 IP - 6 DP - 2006 Dec TI - 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. PG - 1317-24 AB - 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. FAU - Yasuda, Takashi AU - Yasuda T AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kobe University, Kobe 650-0017, Japan. FAU - Kamigaki, Takashi AU - Kamigaki T FAU - Nakamura, Tetsu AU - Nakamura T FAU - Imanishi, Tatsuya AU - Imanishi T FAU - Hayashi, Shun AU - Hayashi S FAU - Kawasaki, Kentaro AU - Kawasaki K FAU - Takase, Shiro AU - Takase S FAU - Ajiki, Tetsuo AU - Ajiki T FAU - Kuroda, Yoshikazu AU - Kuroda Y LA - eng PT - Comparative Study PT - Journal Article PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (Cell Extracts) SB - IM MH - Animals MH - Antigens, Neoplasm/*immunology MH - Apoptosis/physiology MH - Cancer Vaccines/*immunology MH - Cell Extracts/immunology MH - Cell Fusion MH - Colonic Neoplasms/immunology/*therapy MH - Dendritic Cells/*immunology MH - Female MH - Flow Cytometry MH - Hybrid Cells MH - Immunotherapy/*methods MH - Mice MH - Mice, Inbred BALB C MH - Necrosis/physiopathology MH - T-Lymphocytes, Cytotoxic/*immunology EDAT- 2006/11/08 09:00 MHDA- 2006/12/29 09:00 CRDT- 2006/11/08 09:00 PHST- 2006/11/08 09:00 [pubmed] PHST- 2006/12/29 09:00 [medline] PHST- 2006/11/08 09:00 [entrez] PST - ppublish SO - Oncol Rep. 2006 Dec;16(6):1317-24.