Screening of Cytokines to Enhance Vaccine Effects of Heat Shock Protein 70-Rich Tumor Cell Lysate(MEDICAL BIOTECHNOLOGY, <Special Issue>Advances in Biomedical Science and Engineering)

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概要

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• Heat shock proteins (HSPs) have been recognized as significant participants in immune reactions. We have previously reported that heat-treated cells expressing HSP70 can mediate potent antitumor immune responses. As successful immunotherapy is dependent on the host immune system, the present study evaluated whether systemic administration of immunocyte stimulatory and growth promoting cytokines could enhance heat-treated cell lysate vaccine (HCLV) immunization to further promote the antitumor immunity. After heating mouse melanoma B16 cells (43℃, 30min) to elicit increased HSP70 expression, cells were lysed by freeze thawing to prepare HCLV. In approaches using a poorly immunogenic melanoma B16, the effects of various cytokines (IL-1β, -2, -4, -6 and -12, IFN-β and -γ, GM-CSF and TNF-α) were assessed in combination with HCLV. Syngenic C57BL/6 mice were immunized subcutaneously with HCLV twice, on days-14 and -7, while cytokines were injected intraperitoneally on day-7. Subcutaneous B16 cell challenge was performed on day 0.IL-12 significantly enhanced the efficacy of HCLV, compared to non-heated cell lysate vaccine (CLV) and non-vaccination. Systemic administration of recombinant IL-12 augmented the efficacy of HCLV, inducing protective immunity against tumor challenge and enhancing cytotoxicity assessed in primed splenocytes against B16 cells in treated mice. These results suggest that IL-12 represents an important modulator of antitumor immune responses induced by HCLV, and may facilitate further efforts to develop novel cancer immunotherapies based on HSP70-mediated vaccination.

• 社団法人日本生物工学会の論文
• 2005-07-25

著者

• ITO Akira

  Department of Physics, The Cancer Institute, Japanese Foundation for Cancer Research

• Honda Hiroyuki

  Department of Biotechnology, School of Engineering, Nagoya University

• 本多 裕之

  名大院・工・生物機能

• 本多 裕之

  名大院工・生物機能

• Kobayashi T

  School Of Bioscience And Biotechnology Chubu University

• KOBAYASHI Takeshi

  Department of Electrical Engineering, Faculty of Engineering Science, Osaka University

• Kobayasi T

  School Of Bioscience And Biotechnology Chubu University

• Ito A

  The Department Of Computer Science And Systems Engineering Faculty Of Engineering Yamaguchi Universi

• Ito Akira

  Dep. Of Chemical Engineering Fac. Of Engineering Kyushu Univ. 744 Motooka Nishi-ku Fukuoka 819-0395

• Honda Hiroyuki

  Department Of Bioengineering Tokyo Institute Of Technology

• Honda Hiroyuki

  Department Of Biotechnology Graduate School Of Engineering Nagoya University

• Tanaka Kouji

  Department of Biotechnology, School of Engineering, Nagoya University

• Fujioka Masatake

  Department of Biotechnology, School of Engineering, Nagoya University

• Kobayashi T

  Graduate School Of Marine Science And Technology Tokyo University Of Marine Science And Technology

• Fujioka Masatake

  Department Of Biotechnology School Of Engineering Nagoya University

• Ito Akira

  Dep. Of Biochemistry And Molecular Biology Tokyo Univ. Of Pharmacy And Life Sciences School Of Pharm

• Ito Akira

  Department Of Chemical Engineering Faculty Of Engineering Kyushu University

• Ito A

  Kyorin Pharmaceutical Co. Ltd.

• Ito Akira

  Department Of Biochemistry And Molecular Biology School Of Pharmacy Tokyo University Of Pharmacy And

• Ito Akira

  Graduate School Of Engineering Kyushu University

• Ito Akira

  1st Laboratory Of Soil And Fertilizer Environment Division Chugoku National Agricultural Experiment

• Kobayashi Takeshi

  Department Of Biological Chemistry College Of Bioscience And Biotechnology Chubu University

• Kobayashi T

  Dep. Of Biological Mechanisms And Functions Graduate School Of Bioagricultural Sciences Nagoya Univ.

• Tanaka Kouji

  Laboratory Of Genetic Engineering Graduate School Of Agriculture Kyoto Prefectural University

• Kobayashi T

  Graduate School Of Engineering Science Osaka University

• Honda Hiroyuki

  Department Of Anesthesia Niigata City General Hospital

• Ito Akira

  Department Of Chemical Engineering Faculty Of Engineering Kyusyu University

• Tanaka Kouji

  Department Of Biological Function And Genetic Resources Science Faculty Of Agriculture Okayama Unive

• Ito Akira

  Department of Chemical Engineering, Faculty of Engineering, Kyusyu University

• Tanaka Kouji

  Department of Applied Chemistry, Faculty of Engineering, Okayama University

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