Oncolytic adenovirus modified to increase its infectivity for gastrointestinal cancer

• Project/Area Number: 16591381
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Chiba Cancer Research Institute
• Principal Investigator: TAGAWA Masatoshi Chiba Cancer Ctr.Res.Inst., Div. of Path., Head, 病理研究部, 部長 (20171572)
• Co-Investigator(Kenkyū-buntansha): OCHIAI Takenori Graduate School of Chiba Univ., Dept. of Academic Surg., Professor, 大学院・医学研究院・先端応用外科, 教授 (80114255)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000); Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: Gastrointestival tumors / Gene therapy / Transcriptional control region / E1A / E1B region / Oncolytic adenovirus / Fiber region / Suvivin / Shuttle vector / 腫瘍プロモーター / 腫瘍融解性ウイルス / ファイバー・ノブ構造 / サバイビン / ミッドカイン

Research Abstract

Adenovirus (Ad) has a strong cytotoxic activity and the E1A protein, one of the early transcriptional products, has a pivotal role in viral replication in the infected cells. Ad modified to control the E1A gene expression with a putative tumor promoter can thereby be oncolytic. We examined the regulatory regions of the genes which were predominantly expressed in tumors with the luciferase assay and found that a 500 bp and a 600 bp upstream regions of the survivin and midkine genes, respectively, were responsible for the transcriptional control. The cellular receptors of the Ad type 5 is CAR (Coxsackievirus and Adenovirus Receptor) and the expression is often downregulated in gastrointestinal tumors. In contrast, the expression of CD46, which is a receptor of Ad type 35, is rather upregulated in the tumors and consequently, the Ad bearing CD46 binding sites can increase the infectivity to the tumors. We thereby constructed a vector system consisting of vector DNA that could activate the E1A and E1B genes with an exogenous regulatory region and another vector that contained the rest of the whole Ad sequences, in which the fiber-knob region was replaced with the Ad type 35-derived one. In vitro ligation of the vectors enables the construction of the Ad bearing the type 35 fiber-knob structure in the E3 region. The oncolytic Ad with the type 35 fiber-knob can be produced with easy compared with conventional methods that required in vivo recombination. The chimeric oncolytic Ad prepared with our vector system was more cytotoxic to CAR-low human tumors than conventional type 5 oncolytic Ad and was as cytotoxic as the type 5 Ad to CAR-high tumors.

Research Products

• [Journal Article] Vaccination of apoptotic Fas ligand-expressing tumors decreased antitumor responses by enhanced production of immunosuppressive cytokines. (2005)
  • Author(s): Wada A, Tagawa M et al.
  • Journal Title: Anticancer Res. 25 Pages: 299-304
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animals. (2005)
  • Author(s): Chiyo M, Tagawa M et al.
  • Journal Title: Int. J Cancer 115 Pages: 437-442
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] recombinant Sendai virus vector indeces complete remission of established brain tumors trough efficient interleukin-2 gene transfer in vaccinated rats. (2005)
  • Author(s): Iwadata Y, Tagawa M etal.
  • Journal Title: Clin. Cancer Res. 11 Pages: 3821-3827
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Increased infectivity of adenovirus type 5 bearing type 11 or type 35 fibers to human esophageal and oral carcinoma cells. (2005)
  • Author(s): Yu L, Tagawa M et al.
  • Journal Title: Oncol,Rep. 14 Pages: 831-835
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of the fetal-oncogenic fibroblast groeth factor-8/17/18 subfamily in human hematopoietic tumors. (2005)
  • Author(s): Nezu M, Tagawa M et al.
  • Journal Title: Biochem. Biophys. Res. Commun. 335 Pages: 843-849
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Up-regulation of the error-prone DNA polymerase K promotes pleiotropic genetic alterations and tumorigenesis. (2005)
  • Author(s): Bavoux C, Tagawa M et al.
  • Journal Title: Cancer Res. 65 Pages: 325-330
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Vaccination of apoptotic Fas ligand-expressing tumors decreased antitumor responses by enhanced production of immunosuppressive cytokines. (2005)
  • Author(s): Wada, A., Tada, Y., Shimozato, 0., Takiguchi, Y., Tatsumi, K., Kuriyama, T., Tagawa, M.
  • Journal Title: Anticancer Res. 25 Pages: 299-304
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animals. (2005)
  • Author(s): Chiyo, M., Shimozato, O., Yu, L., Kawamura, K., Iizasa, T., Fujisawa, T., Tagawa, M.
  • Journal Title: Int.J.Cancer 115 Pages: 437-442
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Recombinant Sendai virus vector induces complete remission of established brain tumors through efficient interleukin -2 gene transfer in vaccinated rats. (2005)
  • Author(s): Iwadate, Y., Inoue, M., Saegusa, T., Tokusumi, Y., Kinoh, H., Hasegawa, M., Tagawa, M., Yamaura, A., Shimada, H.
  • Journal Title: Clin.Cancer Res. 11 Pages: 3821-3827
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Increased infectivity of adenovirus type 5 bearing type 11 or type 35 fibers to human esophageal and oral carcinoma cells. (2005)
  • Author(s): Yu, L., Takenobu, H., Shimozato, O., Kawamura, K., Nimura, Y., Seki, N., Ugai, K., Tanzawa, H., Shimada, H., Ochiai, T., Tagawa, M
  • Journal Title: Oncol.Rep. 14 Pages: 831-835
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of the fetal-oncogenic fibroblast growth factor-8/17/18 subfamily in human hematopoietic tumors. (2005)
  • Author(s): Nezu, M., Tomonaga, T., Sakai, C., Ishii, A., Itoga, S., Nishimura, M., Matsuo, Y., Tagawa, M., Nomura, F.
  • Journal Title: Biochem.Biophys.Res.Commun. 335 Pages: 843-849
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Up-regulation of the error-prone DNA polymerase x promotes pleiotropic genetic- alterations and tumorigenesis. (2005)
  • Author(s): Bavoux, C., Leopoldino, A.M., Bergoglio, V., O-Wang, J., Ogi, T., Bieth, A., Pena, S.D.J., Poupon, M., Helleday, T., Tagawa, M., Machado, C.R., Hoffmann, J., Cazaux, C.
  • Journal Title: Cancer Res. 65 Pages: 325-330
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Up-regulation of the error-prone DNA polymerase κ promotes pleiotropic genetic alterations and tumorigenesis. (2005)
  • Author(s): Bavoux C, Tagawa M et al.
  • Journal Title: Cancer Res. 65 Pages: 325-330
• [Journal Article] Expression of the fetal-oncogenic fibroblast growth factor-8/17/18 subfamily in human hematopoietic tumors. (2005)
  • Author(s): Nezu M, Tagawa M et al.
  • Journal Title: Biochem.Biophys.Res.Commun 333 Pages: 843-849
• [Journal Article] Increased infectivity of adenovirus type 5 bearing type 11 or type 35 fibers to human esophageal and oral carcinoma cells. (2005)
  • Author(s): Yu L, Tagawa M et al.
  • Journal Title: Oncol.Rep. 14 Pages: 831-835
• [Journal Article] Recombinant Sendai virus vector induces complete remission of established brain tumors through efficient interleukin-2 gene transfer in vaccinated rats. (2005)
  • Author(s): Iwadate Y, Tagawa M et al.
  • Journal Title: Clin.Cancer Res. 11 Pages: 3821-3827
• [Journal Article] Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animals. (2005)
  • Author(s): Chiyo M, Tagawa M et al.
  • Journal Title: Int.J.Cancer 115 Pages: 437-442
• [Journal Article] Vaccination of apoptotic Fas ligand-expressing tumors decreased antitumor responses by enhanced production of immunosuppressive cytokines. (2005)
  • Author(s): Wada A, Tagawa M et al.
  • Journal Title: Anticancer Res 25 Pages: 299-304
• [Journal Article] Insertion of an exogenous progenous promoter in the E1A regulatory of adenovirus dose not disturb viral replication despote reduced E1A transcription. (2004)
  • Author(s): Yu L, Tagawa M et al.
  • Journal Title: Cancer Lett. 203 Pages: 51-57
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of interleukin-21 and -23 in human esphageal tumors produced antitumor sffects in nude mice. (2004)
  • Author(s): Shan B, Tagawa M et al.
  • Journal Title: Anticaner Res. 24 Pages: 79-82
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Midkine promoter can mediate transcriptional activation of a fused suicide gene in a broader range of human breast cancer compared with c-erdB-2 promoter. (2004)
  • Author(s): Yu L, Tagawa M et al.
  • Journal Title: Oncology 66 Pages: 143-146
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Elevated expression of DNA polymerase K expression in human lung cancer is associated with p53 inactivation : Negative regulation of POLK promoter activity by p53. (2004)
  • Author(s): Wang YQ, Tagwa M et al.
  • Journal Title: Int. J. Oncol. 25 Pages: 161-165
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Impaired lymphocyte development and function in Clast5/Stra13/DEC1 transgenic mice. (2004)
  • Author(s): Seimiya M, Tagwa M et al.
  • Journal Title: Eur. J. Immunol. 34 Pages: 1322-1332
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Midkine promoter-driven suicide gene expression and -mediated adenovirus replication produced cytotoxic effects to immortalizad and tumour calls (2004)
  • Author(s): Yu L, Tagawa M et al.
  • Journal Title: Eur.J.Cancer 40 Pages: 1787-1794
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Correlation between interleukin 6 production and tumor proliferation in non-small cell ling (2004)
  • Author(s): Yamaji H, Tagawa M et al.
  • Journal Title: Cancer Immunol. Immunother. 53 Pages: 786-792
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A Cox-2 promoter-based replication-selective adenovital vector to target the Cox-2-expressing human bladder cancer cells. (2004)
  • Author(s): shirakawa T, Tagawa M et al.
  • Journal Title: Clin. Cancer Res. 10 Pages: 4342-4348
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Midkine promoter-based conditinally replicative adenovirus for malignant glioma the rapy. (2004)
  • Author(s): Kohno S, Tagawa M et al.
  • Journal Title: Oncol Rep. 12 Pages: 73-78
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of interleukin-22 in murine carcinoma cells did not influence tumor groeth in vivo but did improve the survival of inoculated hosts. (2004)
  • Author(s): Nagakawa H, Tagawa M et al.
  • Journal Title: Scand. J. Immunol. 60 Pages: 449-454
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Antitumor effects produced by tranduction of dendritic cells-derived heterodimeric cytokine genes in murne colon carcinoma cells. (2004)
  • Author(s): Chiyo M, Tagawa M et al.
  • Journal Title: Anticancer Res. 24 Pages: 3763-3768
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Insertion of an exogenous promoter in the E1A regulatory region of adenovirus does not disturb viral replication despite reduced E1A transcription. (2004)
  • Author(s): Yu, L., Hamada, K., Namba, M., Kadomatsu, K., Muramatsu, T., Matsubara, S., Tagawa, M.
  • Journal Title: Cancer Lett. 203 Pages: 51-57
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of interleukin-21 and -23 in human esophageal tumors produced antitumor effects in nude mice. (2004)
  • Author(s): Shan, B., Yu, L., Shimozato, O., Li, Q., Tagawa, M.
  • Journal Title: Anticancer Res. 24 Pages: 79-82
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Midkine promoter can mediate transcriptional activation of a fused suicide gene in a broader range of human breast cancer compared with c-erbB-2 promoter. (2004)
  • Author(s): Yu, L., Yamamoto, N., Kadomatsu, K., Muramatsu, T., Matsubara, S., Sakiyama S., Tagawa, M.
  • Journal Title: Oncology 66 Pages: 143-146
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Elevated expression of DNA polymerase x expression in human lung cancer is associated with p53 inactivation: Negative regulation of POLKpromoter activity by p53. (2004)
  • Author(s): Wang, Y.Q., Seimiya, M., Kawamura, K., Yu, L., Ogi, T., Takenaga, K., Shishikura, T., Nakagawara, A., Sakiyama, S., Tagawa, M., O-Wang, J.
  • Journal Title: Int.J.Oncol. 25 Pages: 161-165
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Impaired lymphocyte development and function in Clast5/Stra13/DEC1 transgenic mice. (2004)
  • Author(s): Seimiya, M., Wada, A., Kawamura, K., Sakamoto, A., Ohkubo, Y., Okada, S., Hatano, M., Tokuhisa, T., Watanabe, T., Saisho, H., Tagawa, M., O-Wang, J.
  • Journal Title: Eur.J.Immunol. 34 Pages: 1322-1332
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Midkine promoter-driven suicide gene expression and -mediated adenovirus replication produced cytotoxic effects to immortalized and tumour cells. (2004)
  • Author(s): Yu, L., Hamada, K., Namba, M., Kadomatsu, K., Muramatsu, T., Matsubara, S., Tagawa, M.
  • Journal Title: Eur.J.Cancer 40 Pages: 1787-1794
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Correlation between interleukin 6 production and tumor proliferation in non-small cell lung cancer. (2004)
  • Author(s): Yamaji, H., Iizasa, T., Koh, E., Suzuki, M., Otsuji, M., Chang, H., Motohashi, S., Yokoi, S., Hiroshima, K., Tagawa, M., Nakayama, T., Fujisawa T.
  • Journal Title: Cancer Immunol.Immunother. 53 Pages: 786-792
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A Cox-2 promoter-based replication-selective adenoviral vector to target the Cox-2-expressing human bladder cancer cells. (2004)
  • Author(s): Shirakawa, T., Hamada, K., Zhang, Z., Okada, H., Tagawa, M., Kamidono, S., Kawabata, M., Gotoh, A.
  • Journal Title: Cancer Res. 10 Pages: 4342-4348
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Midkine promoter-based conditionally replicative adenovirus for malignant glioma therapy. (2004)
  • Author(s): Kohno, S., Nakagawa, K., Hamada, K., Harada, H., Yamasaki, K., Hashimoto, K., Tagawa, M., Nagato, S., Furukawa, K., Ohnishi, T.
  • Journal Title: Oncol Rep. 12 Pages: 73-78
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of interleukin-22 in murine carcinoma cells did not influence tumor growth in vivo but did improve the survival of inoculated hosts. (2004)
  • Author(s): Nagakawa, H., Shimozato, O., Yu, L., Takiguchi, Y., Tatsumi, K., Kuriyama, T., Tagawa, M.
  • Journal Title: Scand.J.Immunol. 60 Pages: 449-454
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Antitumor effects produced by tranduction of dendritic cells-derived heterodimeric cytokine genes in murine colon carcinoma cells. (2004)
  • Author(s): Chiyo, M., Shimozato, O., Iizasa, T., Fujisawa, T., Tagawa, M.
  • Journal Title: Anticancer Res. 24 Pages: 3763-3768
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Insertion of an exogenous promoter in the E1A regulatory region of adenovirus does not disturb viral replication despite reduced E1A transcription. (2004)
  • Author(s): Yu Ling
  • Journal Title: Cancer Letters 230 Pages: 51-57
• [Journal Article] DNA polymerase θ is preferentially expressed in lymphoid tissues and upregulated in human cancers. (2004)
  • Author(s): Kawamura Kiyoko
  • Journal Title: International Journal of Cancer 109 Pages: 9-16
• [Journal Article] Midkine promoter-driven suicide gene expression and -mediated adenovirus replication produced cytotoxic effects immortalized and tumour cells. (2004)
  • Author(s): Yu Ling
  • Journal Title: European Journal of Cancer 40 Pages: 1787-1794
• [Journal Article] A Cox-2 promoter-based replication-selective adenoviral vector to target the Cox-2-expressing human bladder cancer cells. (2004)
  • Author(s): Shirakawa Toshiro
  • Journal Title: Clinical Cancer Research 10 Pages: 4342-4348
• [Journal Article] Midkine promoter-based conditionally replicative adenovirus for malignant glioma therapy. (2004)
  • Author(s): Kohno Shohei
  • Journal Title: Oncology Report 12 Pages: 73-78
• [Journal Article] Midkine promoter can mediate transcriptional activation of a fused suicide gene in a broader range of human breast cancer compared with c-erbB-2 promoter. (2004)
  • Author(s): Yu Ling
  • Journal Title: Oncology 66 Pages: 143-146