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KMID : 0545120060160121919
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Journal of Microbiology and Biotechnology
2006 Volume.16 No. 12 p.1919 ~ p.1927
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MethA Fibrosarcoma Cells Expressing Membrane-Bound Forms of IL-2 Enhance Antitumor Immunity
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Sonn Chung-Hee
Yoon Hee-Ryung
Seong In-Ock
Chang Mi-Ra
Kim Yong-Chan
Kang Han-Chul
Suh Seok-Cheol
Kim Young-Sang
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Abstract
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Tumor cells genetically engineered to secrete cytokines are effective in tumor therapy, but various unexpected side effects are observed, which may result from the bulk activation of various bystander cells. In this study, we tested tumor vaccines expressing various membrane-bound forms of IL-2 (mbIL-2) on MethA fibrosarcoma cells to focus antitumor immune responses to CTL. Chimeric forms of IL-2 with whole CD4, deletion forms of CD4, and TNF were expressed on the tumor cell surface, respectively. Tumor clones expressing mbIL-2 or secretory form of IL-2 were able to support the cell growth of CTLL-2, an IL-2-dependent T cell line, and the proliferation of spleen cells from 2C TCR transgenic mice that are responsive to the MHC class I complex. Expression of mbIL-2 on tumor cells reduced the tumorigenicity of tumor cells, and the mice that once rejected the live IL-2/TNF tumor clone acquired systemic immunity against wild-type MethA cells. The IL-2/TNF clone was inferior to other clones in tumor formation, and superior in the stimulation of the CD8+ T cell population in vitro. These results suggest that the IL-2/TNF clone is the best tumor vaccine, and may stimulate CD8+ T cells by direct priming. Expression of IL-2/TNF on tumor cells may serve as an effective gene therapy method to ameliorate the side effects encountered in the recombinant cytokine therapy and the conventional cytokine gene therapy using the secretory form of IL-2.
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KEYWORD
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IL-2, membrane-bound form, antitumor immunity, tumor vaccine, direct priming, CTL
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