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

• Published in: Cancer Immunology, Immunotherapy Vol. 56; no. 7; pp. 1025 - 1036
• Main Authors: Yasuda, Takashi, Kamigaki, Takashi, Kawasaki, Kentaro, Nakamura, Tetsu, Yamamoto, Masashi, Kanemitsu, Kiyonori, Takase, Shiro, Kuroda, Daisuke, Kim, Yongsik, Ajiki, Tetsuo, Kuroda, Yoshikazu
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01.07.2007; Springer-Verlag
• Subjects: Adenocarcinoma; Adenocarcinoma - immunology; Adenocarcinoma - therapy; Animals; Antigen (tumor-associated); Antigens, Neoplasm - immunology; Cancer immunotherapy; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Cell Fusion; Colon; Colon cancer; Colonic Neoplasms - immunology; Colonic Neoplasms - therapy; Colorectal cancer; Cytokines; Cytokines - immunology; Cytokines - metabolism; Dendritic cells; Dendritic Cells - immunology; Flow Cytometry; Histocompatibility antigen H-2; Hybrid Cells; Hybrids; Immunization; Immunotherapy; Immunotherapy - methods; Interleukin 10; Intravenous administration; Lymphocytes T; Metastases; Mice; Original; T-Lymphocytes, Cytotoxic - immunology; Transplantation, Homologous; Tumors; β-Galactosidase; γ-Interferon
• ISSN: 0340-7004; 1432-0851; 1365-2567
• DOI: 10.1007/s00262-006-0252-5

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-2(d)) with CT26CL25 colon carcinoma cells that had been fused with either syngeneic DCs from Balb/c mice, allogeneic DCs from C57BL/6 mice (H-2(b)) or semiallogeneic DCs from B6D2F1 mice (H-2(b/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 beta-galactosidase assessed by using pentameric assay. Among the fusion vaccines tested, semiallogeneic DC/TC hybrids induced the highest ratio of Th1 cytokine IFN-gamma 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.