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2002 Fiscal Year Final Research Report Summary

Studies on the generation and application of fusion protein of single chain antibody for P-glycoprotein and chemokine

Research Project

Project/Area Number 13557053
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Respiratory organ internal medicine
Research InstitutionThe University of Tokushima

Principal Investigator

SONE Saburo  The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (40145024)

Co-Investigator(Kenkyū-buntansha) YANO Seiji  The University of Tokushima, University Hospital, Assistant Professor, 医学部附属病院, 講師 (30294672)
NISHIOKA Yasuhiko  The University of Tokushima, School of Medicine, Assistant Professor, 医学部, 講師 (70274199)
TANI Kenji  The University of Tokushima, School of Medicine, Associate Professor, 医学部, 助教授 (70207166)
Project Period (FY) 2001 – 2002
KeywordsMulti-drug resistance / P-glycoprotein / MRK16 / single chain antibody
Research Abstract

The MDR1 gene product P-glycoprotein plays a key role in multidrug resistance of cancer cells. P-glycoprotein is the energy-dependent pump that extrudes a variety of chemotherapeutic drugs. Overexpression of P-glycoprotein results in multidrug resistance of tumor cell lines in vitro as well as in cancer patients. Therefore, much attention has been paid to P-glycoprotein as a molecular target for cancer treatment. MRK16 is the monoclonal antibody against P-glycoprotein and binds to an external domain of P-glycoprotein. It partially inhibits the efflux of certain chemotherapeutic drugs in multidrug-resistant cells, and leads the tumor regression in vivo. Due to the limitations of using intact murine antibodies in human clinical settings, we engineered a single-chain antibody fragment of MRK16 (scFvMRK16). After cloning the variable region of MRK16, both heavy and light chain fragments were fused with linker, and recombinant protein were produced from Escherichia coli. Although the binding activity of scFvMRK16 to P-glycoprotein was 200-300 fold less compared to MRK16, we confirmed by flow cytometric analysis that it does recognize the P-glycoprotein. Furthermore, scFvMRK16 could inhibit the activity of MRK16 to bind P-glycoprotein. These results indicated the therapeutic potential of scFvMRK16.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Nishimura et al.: "Enhanced efficiency by centrifugal manipulation of adenovirus-mediated interleukin 12 gene transduction into human monocyte-derived dendritic cells"Hum Gene Ther. 12. 333-346 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Goto H et al.: "Activity of a new vascular targeting agent, ZD6126, in pulmonary metastases by human lung adenocarcinoma in nude mice"Cancer Res. 62. 3711-3715 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shiraga M et al.: "Organ heterogeneity of host-derived metalloproteinase expression and its involvement in multiple-organ metastasis by lung cancer cell lines"Cancer Res.. 62. 5967-5973 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishioka M et al.: "MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer"P Natl Acad Sci USA. 99・19. 12269-12274 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto A et al.: "A Third-Generation Matrix Metalloproteinase (MMP) Inhibitor (ONO-4817) Combined with Docetaxel Suppresses Progression of Lung Micrometastasis of MMP-Expressing Tumor Cells in Nude Mice"Int J Cancer. 103. 822-828 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishioka Y et al.: "Differential effects of IL-12 on the generation of alloreactive CTL mediated by murine and human dendritic cells : A critical role for nitric oxide"J Leukoc Biol. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishimura, N., Nishioka, Y., Shinohara, T. and Sone, S.: "Enhanced efficiency by centrifugal manipulation of adenovirus-mediated interleukin 12 gene transduction into human monocyte-derived dendritic cells."Hum. Gene Ther.. 12. 333-346 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Goto, H., Yano, S., Zhang, H., Matsumori, Y., Ogawa, H., David C. Blakey., and Sone, S.: "Activity of a New Vascular Targeting Agent, ZD6126, in Pulmonary Metastases by Human Lung Adenocarcinoma in Nude Mice"Cancer Res. 62. 3711-3715 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shiraga, M., Yano, S., Yamamoto, A., Ogawa, H., Goto, H., Miki, T., Miki, K., Zhang, H. and Sone, S.: "Organ Heterogeneity of Host-derived Matrix Metalloproteinase Expression and Its Involvement in Multiple-Organ Metastasis by Lung Cancer Cell Lines"Cancer Res. 62. 5967-5973 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishioka, M., Kohno, T., Tani, M., Yanaihara, N., Tomizawa, Y., Otsuka, A., Sasaki, S., Kobayashi, K., Niki, T., Maeshima, A., Sekido, Y., J.D.Minna., Sone, S. and Yokota, J.: "MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer."PNAS. 99(19). 12269-12274 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto, A., Yano, S., Shiraga, M., Ogawa, H., Goto, H., Miki, T., Zhang, H. and Sone, S.: "A Third-Generation Matrix Metalloproteinase (MMP) Inhibitor (ONO-4817) Combined with Docetaxel Suppresses Progression of Lung Micrometastasis of MMP-Expressing Tumor Cells in Nude Mice"Int J Cancer. 103. 822-828 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishioka Y, Wen H, Mitani K, Robbins PD, Lotze MT, Sone S and Tahara H.: "Differential effects of IL-12 on the generation of alloreactive CTL mediated by murine and human dendritic cells : A critical role for nitric oxide."J Leukoc Biol. (In press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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