Prevention of gastrointestinal tumors based on adenomatous polyposis coli gene mutation by dendritic cell vaccine
Toshio Iinuma, … , Tsuneya Ohno, Gotaro Toda
Toshio Iinuma, … , Tsuneya Ohno, Gotaro Toda
Published May 1, 2004
Citation Information: J Clin Invest. 2004;113(9):1307-1317. https://doi.org/10.1172/JCI17323.
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Prevention of gastrointestinal tumors based on adenomatous polyposis coli gene mutation by dendritic cell vaccine

Abstract

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 APCMin–/+, 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.

Authors

Toshio Iinuma, Sadamu Homma, Tetsuo Noda, Donald Kufe, Tsuneya Ohno, Gotaro Toda

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Effect of treatment with DC/Ts on the development of gastrointestinal tu...
Effect of treatment with DC/Ts on the development of gastrointestinal tumors in APC1309 and APCMin_/+ mice. (A) Ten APC1309 mice were sacrificed at the start of treatment (6 weeks of age). Other groups of APC1309 mice that were untreated or treated with IL-12, with a mixture of PEG-treated DCs and PEG-treated tumor T cells (DC-PEG + T-PEG), with DC/Ts alone, or with DC/T + IL-12, were sacrificed at 10 weeks of age. The gastrointestinal tracts were processed as described in the text. The tumors in the entire gastrointestinal tracts were counted under the microscope. Each column represents mean ± SD (error bar) of the number of tumors. *P < 0.05; **P < 0.001. (B) Six APCMin_/+ mice were sacrificed at the start of treatment (6 weeks of age). Other groups of seven APCMin_/+ mice, which were untreated or treated with IL-12, DC/Ts, or DC/T + IL-12, were sacrificed at 10 weeks of age. The tumors in the entire gastrointestinal tracts were counted as described for A. Each column represents mean ± SD (error bar) of the number of tumors. Figures in parentheses show the number of mice examined. *P < 0.01; **P < 0.001.