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Research Articles: Therapeutics

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

¹ Laboratory of Biomedical Polymer and Tissue Engineering, School of Agricultural Biotechnology and ² Laboratory of Toxicology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, Korea

Requests for reprints: Chong Su Cho, Laboratory of Biomedical Polymer and Tissue Engineering, School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea. Phone: 82-2-880-4636; Fax: 82-2-875-2494. E-mail: chocs{at}plaza.snu.ac.kr or Myung-Haing Cho, Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea. Phone: 82-2-880-1276; Fax: 82-2-873-1268. E-mail: mchotox{at}snu.ac.kr

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-. 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. [Mol Cancer Ther 2006;5(7):1723–32]

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Note: T.H. Kim and H. Jin contributed equally to this work.

Received 12/27/05; revised 4/17/06; accepted 5/17/06.