Innate immunity mediated by dendritic cells/macrophages plays a central role in the early period in tumor treatment using gene of Mycobacterium tuberculosis antigen
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- USHIGUSA Takahiro
- Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka 598-8531 Japan Animal Regerative Medicine Center Hospital, Naka-ku, Yokohama, Kanagawa 231-0033 Japan
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- KOYAMA Yoshiyuki
- Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka 598-8531 Japan Japan Anti-tuberculosis Association, Shin-Yamanote Hospital, Higashimurayama, Tokyo 189-0021 Japan
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- ITO Tomoko
- Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka 598-8531 Japan Japan Anti-tuberculosis Association, Shin-Yamanote Hospital, Higashimurayama, Tokyo 189-0021 Japan
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- WATANABE Kenichi
- Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunyo-ku, Tokyo 113-5657, Japan
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- CHAMBERS James K.
- Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunyo-ku, Tokyo 113-5657, Japan
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- HASEGAWA Aya
- Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka 598-8531 Japan
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- UCHIDA Kazuyuki
- Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunyo-ku, Tokyo 113-5657, Japan
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- KANEGI Ryoji
- Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka 598-8531 Japan
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- HATOYA Shingo
- Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka 598-8531 Japan
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- INABA Toshio
- Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka 598-8531 Japan
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- SUGIURA Kikuya
- Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka 598-8531 Japan
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Abstract
<p>By using a complex of DNA, polyethylenimine and chondroitin sulfate, the in vivo transfection of early secretory antigenic target-6 (ESAT-6) gene into tumor cells was found to cause significant suppression of the tumor growth. In order to apply the method in clinical cancer treatment in dogs and cats, mechanisms underlying the suppressive effects were investigated in a tumor-bearing mouse model. The transfection efficiency was only about 10%, but the transfection of ESAT-6 DNA nevertheless induced systemic immune responses against ESAT-6. By triple injection of ESAT-6 DNA at three day intervals, the tumor was significantly reduced and almost disappeared by 5 days after the start of treatment, and did not increase for more than 15 days after the final treatment. In the immunohistochemistry, a larger number of dendritic cells (DCs)/macrophages expressing ionized calcium-binding adapter molecule 1 and CD3+ T cells was observed in tumors treated with ESAT-6 DNA, and their population further increased significantly by day 5. Moreover, the amount of tumor necrosis factor, which is an apoptosis-inducing factor produced mainly by DCs/macrophages, was greater in the ESAT-6 DNA treated tumors than in controls, and increased with repeat of the treatment. These results indicate that in vivo transfection of ESAT-6 DNA into tumor cells elicits significant inhibition of tumor growth by inducing potent activity of innate immunity mediated by DCs/macrophages, which may be followed by adaptive immunity against tumor associated antigens, elicited by the costimulation with ESAT-6 antigen.</p>
Journal
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- Journal of Veterinary Medical Science
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Journal of Veterinary Medical Science 80 (2), 190-196, 2018
JAPANESE SOCIETY OF VETERINARY SCIENCE
