EBV plasmid vectorを用いたヒト肝細胞癌に対する遺伝子治療の検討

• 研究課題/領域番号: 11670523
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 消化器内科学
• 研究機関: 京都府立医科大学
• 研究代表者: 岩井 眞樹 (岩井 真樹) 京都府立医科大学, 医学部, 助手 (90184853)
• 研究期間 (年度): 1999 – 2000
• 研究課題ステータス: 完了 (2000年度)
• 配分額: 3,400千円 (直接経費: 3,400千円); 2000年度: 800千円 (直接経費: 800千円); 1999年度: 2,600千円 (直接経費: 2,600千円)
• キーワード: 肝細胞癌 / 遺伝子治療 / EBV plasmid vector / 非ウイルスベクター / α-Fetoprotein / 非ウィルスベクター / α-Fctoprotein

研究概要

我々が開発してきたplasmid vectorはEBNA1/oriP systemに自殺遺伝子Herpes simplex virus 1-Thymidine kinase(HSV 1-Tk)を結合し、cationic liposomeやpolyamidoamine dendrimer(PAAD)と組み合わせ、ヒト肝癌細胞株やEwing肉腫に導入し、EBNA1/oriPを除いたcontrol vectorと比較したところ、300〜1000倍もの殺効果を認めた(Y Harada,M Iwai, et al.Cancer Gene Ther 7,27,2000,Hmaruyama-Tabata, et al.Gene Ther 7,53,2000)。
そこでヒトCEA陽性胆管癌細胞株に、同上のsystemにCEAプロモーターを結合させたplasmidをPAADと組み合わせ、投与したところ、強い殺効果が見られた(S Tanaka,M Iwai, et al.Cancer Gene Ther 7,1241,2000)。しかるに、非ウイルスベクターによるEBNA1/oriP systemを用いた自殺遺伝子治療はin vitroのみならずin vivoで殺効果が強く、癌特異的に効果も期待できる事を報告した。今後AFP陽性肝細胞癌に、EBNA1/oriP systemにAFPプロモーターを有するplasmidを用い、検討する予定である。なおgap junctionを介してのbystander effectを研究する目的で、gap junctionの構造、機能についても明らかにした(M Iwai, et al.J Hepatol 32,11,2000)。

研究成果

• [文献書誌] Y Harada,M Iwai, et al.: "Highly efficient suicide gene expression in heterocellular cells by Epskin-Barr Virus-based plasmid vectors combined with polyamidoamine dendrimer"Cancer Gene Ther. 7. 53-60 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] S Tanaka,M Iwai, et al.: "Targeted killing of carcinoembryonic antigen (CEA)-producing cholangiocarcinoma cells by PAMAM dendrimer-mediated transfer of an EBV-based plasmid vector"Cancer Gene Ther. 7. 1241-1249 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] H Maruyama-Tobata,Y Harada,T Matsu nara,E Satoh,F Cui,M Iwai, et al.: "Effective suicide gene therapy in vivo EBV-based plasmid vector coupled with polyamidoamine dendrimer"Gene Ther. 7. 53-60 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] M Iwai, et al.: "Development of gap functional channels and intercellular communication in rat liver during ontogenesis"J Hepatol. 32. 11-18 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Y Harada,H Maruyama-Tabata,E Satoh,M Iwai, et al.: "Superfect reagent-mediated transfection with on EBV-based plasmid vector"Qiagen News. 5. 12-14 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] M Iwai, et al.: "Gene therapy of IL12 for multiple metastatic liver tumors"Hepatology. 32. 179A (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Y Harada, M Iwai, S Tanaka, T Okanoue, K Kashima, H Maruyama-Tabata, H Hirai, E Satoh, J Imanishi, O Mazda: "Highly efficient suicide gene expression in hepatocellular carcinoma cells by Epstein-Barr virus-based plasmid vectors combined with polyamidoamine dendrimer"Cancer Gene Ther. 7. 27-36 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] S Tanaka, M Iwai, Y Harada, T Morikawa, A Muramatsu, T Mori, T Okanoue, K Kashima, H Matuyama-Tabata, H Hirai, E Satoh, J Imanishi, O Mazda: "Targeted killing of carcinoembryonic antigen (CEA)-producing cholangiocarcinoma cells by PAMAM dendrimer-mediated transfer of an Epstein-Barr virus (EBV)-based plasmid vector carrying the CEA-promotor."Cancer Gene Ther. 7. 1241-1249 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] H Maruyama-Tabata, Y Harada, T Matsumura, E Satoh, F Cui, M Iwai, M Kita, S Hibi, J Imanishi, T Sawada, O Mazda: "Effective suicide gene therapy in vivo by EBV-based plasmid vector coupled with polyamidoamine dendrimer."Gene Ther. 7. 53-60 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] M Iwai, Y Harada, A Muramatsu, S Tanaka, T Mori, T Okanoue, F Katoh, T Ohkusa, K Kashima.: "Development of gap junctional channels and intercellular communication in rat liver during ontogenesis."J Hepatol. 32. 11-18 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Y Harada, H Maruyama-Tabata, E Satoh, M Iwai, J Imanishi, O Mazda: "Superfect reagent-mediated transfection with an EBV-based-plasmid vector"Qiagen News. 5. 12-14 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] M Iwai, T Mori, A Muramatsu, T Morikawa, Y Harada, T Okanoue, K Kashima: "Gene therapy of IL12 for multiple metastatic liver tumors"Hepatology. 32. 179A (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] M Iwai, T Morikawa, A Muramatsu, S Tanaka, T Mori, Y Harada, T Okanoue, K Kashima., M Ishii: "Biological significance of AFP expression in liver injury induced by CCl_4."Acta histochem cytochem. 33. 17-22 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Tanaka S,Iwai M, et.al.: "Targeted killing of CEA producing CCC cells by PAMAM dendrimer mediated transfer of an EBV"Cancer Gene Ther. 7. 1241-1249 (2000)
• [文献書誌] Harada Y,Iwai M, et al.: "Highly efficient suicide gene expression in hepato-cellular carcinoma cells by EBV-based plasmid"Cancer Gene Ther. 7. 27-36 (2000)
• [文献書誌] Iwai M,Morikawa T, et al.: "Biological significance of AFP expression in liver injury induced by CC14"Acta histochem cytochem. 33. 17-22 (2000)
• [文献書誌] Harada Y,Iwai M, et al.: "Superfect reagent-mediated transfection with an EBV based-plasmid vector"Qiagen News. 5. 12-14 (2000)
• [文献書誌] Morikawa T,Iwai M, et al.: "Suicide gene therapy for HCC in vivo by means of EBV-based plasmid vector/polyethylenimine"JSGT. 6. 134 (2000)
• [文献書誌] Iwai M,Mori T, et.al.: "Gene therapy of IL12 for multiple metastatic liver tumors"Hapatology. 32・4. 179A (2000)
• [文献書誌] M.Iwai,et al.: "Development of gap junctional channels and inter-celluler communication in rat liverduring ontogenesis"J Hepatol. 32. 11-18 (2000)
• [文献書誌] Y Harada,M.Iwai,et al.: "Highly efficient suicide gene expression in hepatocellular carcinoma cells by Epokin-Batrrincs-based plasmid〜"Cancer Gene Therapy. 7. 27-36 (2000)
• [文献書誌] Hiroko Maruyama Tabata,et al.: "Effective suicide gene therapy in vivo by ERV-based plasmid vector coupled with polyamido amine〜"Gene Therapy. 7. 53-60 (2000)
• [文献書誌] M Iwai et al.: "Cholestatic ** in two patients with primary amyloidosis-Ultrastructural tihadiys〜"J Clin Gastroenteral. 28(2). 162-166 (1999)
• [文献書誌] T Mori,M Iwai,et al.: "Parenclymal cells proliferate and differentiate in an organotypic slice culture of the neonatal liver"Anat Embryol. 199. 319-327 (1999)