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Mannosylated chitosan nanoparticle–based cytokine gene therapy suppressed cancer growth in BALB/c mice bearing CT-26 carcinoma cells

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Authors
Kim, Tae Hee; Jin, Hua; Kim, Hyun Woo; Cho, Myung-Haing; Cho, Chong Su
Issue Date
2006
Publisher
American Association for Cancer Research
Citation
Mol Cancer Ther 2006;5:1723-1732
Keywords
cytokine gene therapyIL-12mannosylated chitosan nanoparticledendritic cells
Abstract
Cancer immunotherapy relies on the ability of the immune system to destroy tumor cells selectively and to elicit a long-lasting memory of such activity. Interleukin-12 (IL-12) is an immunomodulatory cytokine produced primarily by antigen-presenting cells, which play an important role in promoting Th1-type immune response and cell-mediated immunity. To augment the antitumor immune action by in vivo IL-12 gene delivery, mannosylated chitosan (MC) was prepared to induce mannose receptor–mediated endocytosis of IL-12 gene directly into dendritic cells which reside within the tumor. Upon characterization, MC was proven to be suitable for IL-12 gene delivery due to good physicochemical properties and low cytotoxicity. In addition, MC exhibited much enhanced IL-12 gene transfer efficiency to dendritic cells rather than chitosan itself in terms of the induction of murine IL-12 p70 and murine IFN-γ. In animal studies, intratumoral injection of MC/plasmid encoding murine IL-12 complex into BALB/c mice bearing CT-26 carcinoma cells clearly suppressed tumor growth and angiogenesis, and significantly induced cell cycle arrest and apoptosis. Therefore, this study provides a new MC-mediated cytokine gene delivery system for cancer immunotherapy.
ISSN
1535-7163
Language
English
URI
http://hdl.handle.net/10371/6524
DOI
https://doi.org/10.1158/1535-7163.MCT-05-0540
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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