2002 Fiscal Year Final Research Report Summary
Gene therapy for gastrointestinal tumors using antigen presenting cells activated with gene transfer
| Project/Area Number |
13671367
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Chiba Cancer Center Research Institute |
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Principal Investigator |
TAGAWA Masatoshi Chiba Cancer Center Research Institute Division of Pathology Head, 病理研究部, 部長 (20171572)
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| Co-Investigator(Kenkyū-buntansha) |
OCHIAI Takenori Chiba University, Graduate School of Medicine Academic Surgery Professor, 大学院・医学研究院・先端応用外科学, 教授 (80114255)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Gene therapy / CD40 ligand / CD40 / dendritic cells / protective immunity / IL-12 / CD86 / Mig |
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| Research Abstract |
We examined whether professional antigen presenting cells (dendritic cells) could be activated by the expression of CD40 ligand (CD40L) gene on tumors and antitumor immunity was subsequently induced. We retrovirally transduced tumors with the CD40L gene and established CD40L-expressed tumors whose MHC class I expression remained the same as that of parent tumors. Inoculation of the transduced cells into syngeneic mice revealed that growth of CD40L-expressed tumors was significantly retarded compared with that of parent tumors. Some of the mice completely rejected the CD40L-expressed tumors and the mice developed antigen-specific protective immunity. When nude mice were inoculated with the CD40L-expressed tumors, the growth was not different from that of parent tumors. In vitro culture of the CD40L-expressed tumors and bone marrow-derived dendritic cells showed that the cluster formation between dendritic cells and the CD40L-expressed but not parent tumors. The expression of MHC class II and activation marker CD86 on dendritic cells was upregulated after the coculture with CD40L-expressed but not parent tumors. The activated dendritic cells secreted IL-12, IL-18, IL-23 and Mig. These data collectively suggest that CD40L on tumors can activate dendritic cells through CD40/CD40L interaction and induce the expression of cytokines and chemokines, which play a crucial role in the generation of T cell-mediated antitumor effects.
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Research Products
(24 results)
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[Publications] Kawamura, K., Bahar, R., Namba, H., Seimiya, M.,Takenaga, K., Hamada, H., Sakiyama, S. and Tagawa,M.: "Bystander effect in uracil phosphoribosyltransferase/5-fluorouracil-mediated suicide gene therapy is correlated with the level of intercellular communication"Int. J. Oncol.. 18. 117-120 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Matsubara, H., Maeda, T., Gunji, Y., Koide, Y., Asano,T., Ochiai, T., Sakiyama, S. and Tagawa, M.: "Combinatory anti-tumor effects of electroporation-mediated chemotherapy and wild-type p53 gene transfer to human esophageal cancer cells"Int. J. Oncol.. 18. 825-829 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Matsubara, H., Gunji, Y., Maeda, T., Tasaki, K., Koide,Y., Asano, T., Ochiai, T., Sakiyama, S. and Tagawa, M.: "Electroporation-mediated transfer of cytokine genes into human esophageal tumors produces anti-tumor effects in mice"Anticancer Res.. 21. 2501-2504 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Miyauchi, M., Yoshida, Y., Tada, Y., Narita, M., Maeda, T., Bahar, R., Kadomatsu, K., Muramatsu, T., Matsubara, S., Nakagawara, A., Sakiyama, S. and Tagawa, M.: "Expression of herpes simplex virus-thymidine kinase gene controlled by a promoter region of the midkine gene confers selective cytotoxicity to ganciclovir in human carcinoma cells"Int. J. Cancer. 91. 723-727 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tada, Y., O-Wang, J., Takiguchi, Y., Tatsumi, K.,Kuriyama, T. and Tagawa, M.: "T cell dependent and independent antitumor immunity generated by the expression of Fas ligand on mouse lung carcinoma cells"Int. J. Mol. Med.. 9. 281-285 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Yoshida, Y., Tomizawa, M., Bahar, R., Miyauchi, M., Yamaguchi, T., Saisho, H., Kadomatsu, K., Muramatsu, T., Matsubara, S., Sakiyama, S. and Tagawa, M.: "A promoter region of midkine gene can activate transcription of an exogenous suicide gene in human pancreatic cancer"Anticancer Res.. 22. 117-120 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tada, Y., O-Wang, J., Takenaga, K., Takiguchi, Y., Tatsumi, K., Kuriyama, T. and Tagawa, M.: "Expression of the TNF-α gene on mouse lung carcinoma cells suppresses spontaneous lung metastasis without affecting tumorigenicity"Oncol. Rep.. 9. 585-588 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tomizawa, M., Wang, Y-Q., Ebara, M, Saisho, H., Watanabe, K., Nakagawara, A. and Tagawa, M.: "Decreased expression of the CCAAT/enhancer binding protein α gene involved in hepatocyte proliferation in human hepatocellular carcinoma"Int. J. Mol. Med.. 9. 597-600 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Tada, Y., O-Wang, J., Takiguchi, Y., Tatsumi, K., Kuriyama, T., Okada, S., Tokuhisa, T., Sakiyama, S. and Tagawa, M.: "A novel role for Fas ligand in facilitating antigen acquisition by dendritic cells"J. Immunol.. 169. 2241-2245 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Tada, Y., O-Wang, J., Seimiya, M., Takiguchi, Y., Tatsumi, K., Kuriyama, T. and Tagawa, M.: "Antitumor effects are produced by forced expression of membrane-bound but not soluble Fas ligand in murine lung carcinoma cells"Anticancer Res.. 22. 831-836 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Tada, Y., O-Wang, J., Yu, L., Shimozato, O., Wang, Y-Q., Takiguchi, Y., Tatsumi, K., Kuriyama, T., Takenaga, K., Sakiyama, S. and Tagawa, M.: "T cell-dependent antitumor effects produced by CD40 ligand expressed on mouse lung carcinoma cells are linked with the maturation of dendritic cells and secretion of a variety of cytokines"(in press).
Description
「研究成果報告書概要(欧文)」より
