Prevention of gastrointestinal tumors based on adenomatous polyposis coli gene mutation by dendritic cell vaccine.
Here we describe the effect of immunization with dendritic cells loaded with syngeneic tumor cells (DC/Ts) by polyethylene glycol treatment, on tumor development in adenomatous polyposis coli (APC) gene mutant mouse models, APC1309 and APC(Min-/+), in which adenomatous polyps of the gastrointestinal tracts develop with a high incidence. Treatment with DC/Ts prevented the development of gastrointestinal tumors, and coadministration of DC/Ts and IL-12 caused a further reduction in tumor incidence. Splenocytes from APC1309 mice treated with DC/Ts and IL-12 showed no cytotoxic activity toward the tumor cells, but serum antibody specific to them was detected. IgG from the treated mice exhibited cytotoxic activity against the tumor cells in vitro. Predominance of Th2 cell response over Th1 response was also suggested by ELISPOT assays in the treated mice. Depletion in vivo of CD4(+) T cells, not CD8(+) T cells, by the intraperitoneal administration of corresponding mAb's decreased the antitumor effect of DC/T inoculation. Immunofluorescence microscopic studies showed that Ig was attached to tumor cells in mice treated with DC/Ts and IL-12. These findings indicate that DC/T vaccination prevents tumor development through APC gene mutation and that its preventive effects are mediated by humoral antitumor immunity.
Iinuma
Toshio
T
Department of Internal Medicine, Jikei University School of Medicine, Minato-ku, Tokyo, Japan. t.iinuma@jikei.ac.jp
Homma
Sadamu
S
Noda
Tetsuo
T
Kufe
Donald
D
Ohno
Tsuneya
T
Toda
Gotaro
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D005770:Gastrointestinal Neoplasms / Q000473:pathology / Q000517:prevention & control*; D017491:Genes, APC; D018664:Interleukin-12 / Q000627:therapeutic use; D008546:Melanoma, Experimental / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D018664:Interleukin-12