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Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma

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Abstract

Cancer immunotherapy by dendritic cell (DC)/tumor cell fusion hybrids (DC/TC hybrids) has been shown to elicit potent anti-tumor effects via the induction of immune responses against multiple tumor-associated antigens. In the present study, we compared the anti-tumor effects of vaccinating Balb/c mice (H-2d) with CT26CL25 colon carcinoma cells that had been fused with either syngeneic DCs from Balb/c mice, allogeneic DCs from C57BL/6 mice (H-2b) or semiallogeneic DCs from B6D2F1 mice (H-2b/d). Preimmunization with either semiallogeneic or allogeneic DC/TC hybrids induced complete protection from tumor challenge, whereas mice preimmunized with syngeneic DC/TC hybrids were only partially protected (75% tumor rejection). The average number of pulmonary metastases after intravenous tumor injection decreased significantly following immunization with semiallogeneic or allogeneic DC/TC hybrids (8.3 ± 7.9 or 16.3 ± 3.5, mean ± SD) relative to syngeneic DC/TC hybrids (67.8 ± 6.3). These data demonstrate that vaccination with semiallogeneic DC/TC hybrids resulted in the greatest anti-tumor efficacy. Anti-tumor effects showed by in vivo studies were virtually accomplished by the frequency of induced CTLs specific to both gp70 and β-galactosidase assessed by using pentameric assay. Among the fusion vaccines tested, semiallogeneic DC/TC hybrids induced the highest ratio of Th1 cytokine IFN-γ to Th2 cytokine IL-10. In addition, allogeneic or semiallogeneic DC/TC hybrids elicited a significantly stronger NK activity than syngeneic DC/TC hybrids. These findings suggest that in clinical settings, DCs derived from a healthy donor (which are generally characterized as more semiallogeneic than allogeneic) may be more capable than autologous DCs of inducing promising anti-tumor effects in vaccinations with DC/TC hybrids.

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Abbreviations

DC:

Dendritic cell

TC:

Tumor cell

APC:

Antigen-presenting cell

FSC:

Forward scatter

SSC:

Side scatter

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kobe University, Kusunoki-cho 7-5-1, Chuo-ku, Kobe, 650-0017, Japan

    Takashi Yasuda, Takashi Kamigaki, Kentaro Kawasaki, Tetsu Nakamura, Masashi Yamamoto, Kiyonori Kanemitsu, Shiro Takase, Daisuke Kuroda, Yongsik Kim, Tetsuo Ajiki & Yoshikazu Kuroda

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  1. Takashi Yasuda
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  2. Takashi Kamigaki
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  3. Kentaro Kawasaki
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Correspondence to Takashi Yasuda.

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Yasuda, T., Kamigaki, T., Kawasaki, K. et al. Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma. Cancer Immunol Immunother 56, 1025–1036 (2007). https://doi.org/10.1007/s00262-006-0252-5

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