Cancer Immunology, Immunotherapy

, Volume 56, Issue 7, pp 1025–1036

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

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

DOI: 10.1007/s00262-006-0252-5

Cite this article as:
Yasuda, T., Kamigaki, T., Kawasaki, K. et al. Cancer Immunol Immunother (2007) 56: 1025. doi:10.1007/s00262-006-0252-5

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.

Keywords

DC and tumor cell fusion hybrids Allogeneic and semiallogeneic DC Pentamer staining Th1/Th2 cytokines Tumor immunity 

Abbreviations

DC

Dendritic cell

TC

Tumor cell

APC

Antigen-presenting cell

FSC

Forward scatter

SSC

Side scatter

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Takashi Yasuda
    • 1
  • Takashi Kamigaki
    • 1
  • Kentaro Kawasaki
    • 1
  • Tetsu Nakamura
    • 1
  • Masashi Yamamoto
    • 1
  • Kiyonori Kanemitsu
    • 1
  • Shiro Takase
    • 1
  • Daisuke Kuroda
    • 1
  • Yongsik Kim
    • 1
  • Tetsuo Ajiki
    • 1
  • Yoshikazu Kuroda
    • 1
  1. 1.Department of Gastroenterological Surgery, Graduate School of Medical SciencesKobe UniversityKobeJapan

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