Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma.
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.
Yasuda
Takashi
T
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kobe University, Kusunoki-cho 7-5-1, Chuo-ku, Kobe 650-0017, Japan. yasudatyamane@yahoo.co.jp
Kamigaki
Takashi
T
Kawasaki
Kentaro
K
Nakamura
Tetsu
T
Yamamoto
Masashi
M
Kanemitsu
Kiyonori
K
Takase
Shiro
S
Kuroda
Daisuke
D
Kim
Yongsik
Y
Ajiki
Tetsuo
T
Kuroda
Yoshikazu
Y
D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002459:Cell Fusion; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006822:Hybrid Cells; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines