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1998 Fiscal Year Final Research Report Summary

Development for new transduction of gene by using mouse monoclonal antibody or its humanized antibody

Research Project

Project/Area Number 08457363
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionOsaka University

Principal Investigator

SHIMIZU Keiji  Osaka University Medical School, Associate Professor, 医学部, 助教授 (50162699)

Co-Investigator(Kenkyū-buntansha) IKENAKA Kazuhiro  Okazaki National Research Institutes, Professor, 生理学研究所, 教授 (00144527)
MIYAO Yasuyoshi  Osaka University Hospital, Medical Stuff, 医学部・附属病院, 医員
Project Period (FY) 1996 – 1998
KeywordsMonoclonal antibody / Humanized antibody / Single-chained antibody / Gene therapy / Gene transfer / HVJ-liposome / Immunoliposome / Intemalization
Research Abstract

The glioma-associated antigen, which mouse monoclonal antibody ONS-M21 (Br J Cancer, 1999) recognized, was integrin alpha3. The expression of integrin alpha3 in the normal brain has been reported to be very low or even undetectable. It appears that the level of this antigen expressed in glioma is correlated with the grade of malignancy and invasion. It is, therefore, very important to investigate integrin alpha3 in glioma cells in order to expect the prognosis of their patients. On the other hand, in the experimental gene therapy of glioma with retroviral vectors reconstructed brain-specific promoter, myelin basic protein (MBP) promoter (Hum Gene Ther, 1997 ; Gene Ther, 1998), it is demonstrated that mouse glioma models were completely recovered with intraperitoneal administration of ganciclovir (GCV), if herpes simplex thymidine kinase (HTK) could be introduced into about 25 % of glioma cells. To obtain high-titer recombinant retroviruses, we constructed plasmid pDL^#, which carries t … More he extended Psi region and the polyomavirus early region, including the replication origin and the early gene. Then we modified the packaging cell lines, PA317, by stably introducing the polyomavirus early gene, and established PAMP5 1 from PA317 cells (Hum Gene Ther, 1998). In vivo experiments by using these high-titer recombinant retroviruses, 80 % of mouse glioma models were completely recovered (Hum Gene Ther, in submitted). In this way we could get very effective vectors, but we could not get therapeutic effects at all by these vectors, if tumor does not have retrovirus receptors. For the tumors that did not have these receptors, we investigated the delivery of HTK genes into glioma cells in vivo using hemagglutinating virus of Japan (HVJ)-liposomes, which are coated by Sendai virus envelope protein. Highly efficient delivery was observed in disseminated glioma cells of MG mice, and 8O0/c of these mice expressing the HTK gene were cured by administration of GCV (Gene Ther, 1997). And moreover, we will thoroughly investigate more specific gene therapy for glioma by HVJ liposome-binding humanized (Mol Immunol, 1995) or single-chain antibodies (Anticancer Res, 1998). When humans medulloblastoma ONS-76 cells were co-cultured with ONS-M21 antibodies, about 20% antibodies were internalized into these cells for less than 30 minutes (Cancer lett, 1998). A cytotoxic effect against ONS-76 cells was found by the iminunotoxin which was bounded with ricin A chain and ONS-M21 antibodies, but not against antigen-negative human hepatoma HuH-7 and colon cancer SW480 cells. These results suggest that ONS-M2 I antibodies could effectively deliver toxins, chemotherapeutic agents or radionuclei to malignant glioma specifically. Now we, however, try to transduce HTK genes into the glioma cells by installments, because the molecular weight of HTK genes-binding ONS-M21 is too big to introduce HTK gene complex by the lump. Less

  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Moriuchi S: "Decreased N-myc expression in human medulloblastoma cell lines during differentiation." Anticancer Res. 17(1). 301-306 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura M: "Targeted killing of migrating glioma cells by injection of HTK-modified glioma cells." Hum Gene Ther. 8(3). 381-391 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyao Y: "Usefulness of a mouse myelin basic protein promoter for gene therapy of malignant glioma : myelin basic protein promoter is strongly active in human malignant glioma cells." Jpn J Cancer Res. 88(7). 678-686 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mabuchi E: "Gene delivery by HVJ-liposome in the experimental gene therapy of murine glioma." Gene Ther. 4(8). 768-772 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyao Y: "FT-175, a synthetic inhibitor of the complement pathway, protects against the inactivation of infectious retrovirus by human serum." Hum Gene Ther. 8(9). 1575-1583 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimizu K: "Internalization with hige tergeting potential of mouse monoclonal-antibody ons-M21 recognizing human-malignat glioma antigen." 127(1-2). 171-176 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Park KC: "Regulation of interferon responses in medulloblastoma cells by interferon regulatory factor-1 and -2" Br J Cancer. 77(12). 2081-2087 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura M: "Transduction of glioma cells using a high titer retroviral vector system and their subsequent migration in brain tunor." Gene Ther. 5(12). 1698-1704 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohtomo T: "A humanized single-chain Fv fragment with highly targeting potential against human malignant gliomas." Anticancer Res. 18(12). 4311-4315 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kishima H: "Monoclonal antibody ONS-M21 recognizes integrin α3 in gliomas and medulloblastomas." Br J Cancer. 79(2). 333-339 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyao Y: "Brain Tumor Research and Therapy" Springer-Verlag Tokyo, 456 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Moriuchi S: "Decreased N-myc expression in human medulloblastoma cell lines during differentiation." Antiancer Res. 17(1). 301-306 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura M: "Targeted killing of migrating glioma cells by injection of HTK-modified glioma cells." Hum Gene Ther. 8(3). 381-391 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyao Y: "Usefulness of a mouse myelin basic protein promoter for gene therapy of malignant glioma : myelin basic protein promoter is strongly active in human malignant glioma cells." Jpn J Cancer Res. 88(7). 678-686 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mabuchi E: "Gene delivery by HVJ-liposome in the experimental gene therapy of murine glioma." Gene Ther. 4(8). 768-772 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyao Y: "FT-175, a synthetic inhibitor of the complement pathway, protects against the inactivation of infectious retrovirus by human serum." Hum Gene Ther. 8(9). 1575-1583 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizu K: "Internalization with high targeting potential of mouse monoclonal antibody ONS-M21 recognizing human malignant glioma antigen." Cancer lett. 127(1-2). 171-176 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Park KC: "Regulation of interferon responses in medulloblastoma cells by interferon regulatory factor-1 and-2." Br J Cancer. 77(12). 2081-2087 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura M: "Transduction of glioma cells using a high titer retroviral vector system and their subsequent migration in brain tumor." Gene Ther. 5(12). 1698-1704 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohtomo T: "A humanized single-chain Fv fragment with highly targeting potential against human malignant gliomas." Anticancer Res. 18(12). 4311-4315 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kishima H: "Monoclonal antibody ONS-M21 recognizes integrin alpha3 in gliomas and medulloblastomas." Br J Cancer. 79(2). 333-339 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyao Y: Brain Tumor Research and Therapy, Nagai M(ed), Springer-Verlag Tokyo. Investigations of retroviral-mediated gene therapy for malignant glioma : Transduction with HTK-bearing retroviruses sensitizes glioma cells to ganciclovir., 456 (1996)

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

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Published: 1999-12-08  

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