• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

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
田村 和義  大阪大学, 医学部附属病院, 医員
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1996: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsMonoclonal antibody / Humanized antibody / Single-chained antibody / Gene therapy / Gene transfer / HVJ-liposome / Immunoliposome / Intemalization / HVJ-lioposome / Intermalization
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

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (52 results)

All Other

All Publications (52 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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Related Report
      1998 Annual Research Report
  • [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)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tamura M: "Transduction of glioma cells using a high titer retroviral system and their subsequent migration in brain tumor." Gene Ther. 5(12). 1698-1704 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohtomo T: "A humanized single-chain Fv fragment with highly targeting potential against human malignant gliomas." Anticancer Res. 18(12). 4311-4315 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kishima H: "Monoclonal antibody ONS-M21 recognizes integrin α3 in gliomas and medulloblastomas." Br J Cancer. 79(2). 333-339 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Moriuchi S: "An Immunohistochemical Analysis of Medulloblastoma and PNET with Emphasis on N-myc Protein Expression." Anticancer Res. 16. 2687-2692 (1996)

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

    • Related Report
      1997 Annual Research Report
  • [Publications] Tamura M: "Targeted killing of migrating glioma cells by injection of HTK-modified glioma cells." Hum Gene Ther. 8. 381-391 (1997)

    • Related Report
      1997 Annual Research Report
  • [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. 678-686 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mabuchi E: "Gene delivery by HVJ-liposome in the experimental gene therapy of murine glioma." Gene Ther. 4. 768-772 (1997)

    • Related Report
      1997 Annual Research Report
  • [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. 1575-1583 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kishima H: "Possible common origin of α-fetoprotein-and human chorionic gonadotropin-secreting cells in intracranial germ cell tumor." J Neurosurg. 88. 576-580 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Park KC: "Interferon yield MHC antigen expression of human medulloblastoma cells and its suppression during dibutyryl cyclic AMP-induced differentiation :" Cell Mol Neurobiol. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamada M: "In vitro study on intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) for meningeal dissemination of malignant brain tumors." J Neuro-oncol. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Park KC: "Regulation of interferon responses in medulloblastoma cells by interferon regulatory factor -1 and -2." Br J Cancer. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shimizu K: "Internalization with high targeting potential of mouse monoclonal antibody ONS-M21 recognizing human malignant glioma antigen." Cancer lett. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kishima H: "Systemic interleukin-12 displays antitumor activity in the mouse central nervous system." Br J Cancer. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamaguchi Y: "Myelin proteolipid protein (PLP),but not DM-20,is an inositol hexakisphosphate binding protein." J Biol Chem. 271. 27838-27846 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikeda H: "Retroviral introduction of the p16 gene into murine cell lines to elicit marked antiproliferative effects." Jpn.J Cancer Res. 88. 712-717 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Baba H: "GFAP gene expression during development of astrocyte." Dev Neurosci. 19. 49-57 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Morita N: "Astrocytic lineage analysis by detection of GFAP promoter activity in vitro." Dev Neurosci. 19. 210-218 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshimatsu T: "Improvement of retroviral packaging cell lines by introducing the polymavirus early region." Hum Gene Ther. 9. 161-172 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyao Y: "Brain Tumor Research and Therapy" Nagai M (ed),Springer-Verlag Tokyo,(Japan), 456 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Moriuchi S: "In vitro Assessments for Neurotoxicity of Antitumor Agents before Local Administration into Central Nervous Systems." Anticancer Res. 16. 135-140 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Moriuchi S: "An Immunohistochemical Analysis of Medulloblastoma and PNET with Emphasis on N-myc Protein Expression." Anticancer Res. 16. 2687-2692 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Moriuchi S: "Decreased N-myc expression in human medulloblastoma cell lines during differentiation." Anticancer Res (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Tamura M: "Targeted killing of migrating glioma cells by injection of HTK-modified glioma cells." Hum Gene Ther (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Mabuchi E: "Gene delivery by HVJ-liposome in the experimental gene therapy of murine glioma." Gene Ther (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Miyao Y: "Brain Tumor Research and Therapy" Springer-Verlag Tokyo, 456 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 馬淵英一郎: "神経免疫研究 第9巻" 「脳と免疫」研究会, 288 (1996)

    • Related Report
      1996 Annual Research Report

URL: 

Published: 1996-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi