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Novel Anti-Cancer Drug Composed of Human Proteins

Research Project

Project/Area Number 07457262
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKeio University

Principal Investigator

UEDA Masakazu  Keio Univ., School of Medicine Surgery, Assistante Professor, 医学部, 講師 (50142419)

Co-Investigator(Kenkyū-buntansha) TAKESHIMA Kaoru  Keio Univ., School of Medicine Surgery, Assistant, 医学部, 助手 (50236460)
JINNO Hiromitsu  Keio Univ., School of Medicine Surgery, Assistant, 医学部, 助手 (20216261)
KIKUCHI Kiyoshi  Keio Univ., Cancer Center, Assistant, がんセンター, 助手 (30129407)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1996: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsAnti-cancer druo / EGF / RNase / immunotoxin / EGFreceptor / ヒト生理活性物質 / 扁平上皮癌 / 乳癌 / ミサイル療法 / リコンビナントタンパク
Research Abstract

1. Mammalian pancreatic robonuclease (RNase) was conjugated chemically via a disulfide bond to human epidermal growth factor (EGF). The human EGF-mam malian RNase conjugate had no cytotoxic effect against the EGFreceptor-deficient small-cell lung cancer cell line H69. But this conjugate showed dose-dependent cytotoxicity against squamous carcinoma cell lines and breast cancer cell lines and the cytotoxicity of the conjugate correlated positively with the level of expression of EGFR by each cell line. An unconjugated mixture of EGF and RNase had no greater effect than RNase alone on any cell lines.
2. Recombinant human RNase 1 (RNase1) was chemically linked to recombinant human EGF.The EGF-RNase conjugate showed dose-dependent cytotoxicity for EGF receptor-overexpressing cell lines. An unconjugated mixture of EGF and RNase had no greater effect than RNase alone. the conjugate showed no detectable cytotoxicity atainst EGF receptor-deficient small cell lung cancer cell.
3. The gene coding for human pancreatic RNase1, was fused with a gene coding for human EGF or human IL-2. These DNA were expressed in E.Coli, efficient amounts of the recombinant human protein were produced in inclusion bodies, solubilized, refolded in vitro, regained activity and purified to homogeneity.
4. The RNase-EGF conjugate was cytotoxic, EGF-receptor number dependently, to several squamous carcinoma cell lines. A mixture of free EGF and free RNase1 had no greater effect than RNase1 alone and no cytotoxicity was detectable for receptor deficient control cells.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report

Research Products

(24 results)

All Other

All Publications (24 results)

  • [Publications] Kaneta Y.,et al.: "Effects of gelonin conjugate with monoclonal antibody MSN-1 and endometrial adnocarcinoma in vitro." Oncology Report. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ikeda Y.,et al.: "Meanings of c-erb B and int-2 oncogene amplitication in the patients with superficial esophageal squamous cell Garcinomasa." Annals of thoracic surgery. 62. 835-858 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Jinno H.,et al.: "Effect of an adriamvcin-immunoconjugate that recognizes the c-erb R product on breast cancer cell lines." Surgery Today. 26. 501-507 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tada H.,et al.: "Human betacellulin & member of the EGF family dominantly expressed in pancrease and small intestine is fully acti in a monomeric from." Growth Factor. 13. 181-191 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Jinno H.,et al.: "EGF receptor-dependent cytotoxicity for human squamous cell carcinoma cell lines of a conjugate composed of human protein." Life Science. 58. 1901-1908 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Jinno H.,et al.: "EGF receptor-dependent cytotoxic effect by EGF-RNase conjugate on human cancer cell lines." Cancer Chemotherapy and Pharmacology. 38. 303-308 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kaneta Y., et.al.: "Effects of gelonin conjugate with monoclonal antibody MSN-1 and endometrial adenocarcinoma in vitro." Oncology Report. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ikeda Y., et.al.: "Meanings of c-erb R and int-2 oncogene amplification in the patients with superficial esophageal squamous cell carcinoma" Annals of thoracic Surgery. 62. 835-858 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Jinno H., et.al.: "Effect of an adriamycin-immuno-conjugate that recognizes the c-erb R product on breast cancer cell lines." Surgery Today. 26. 501-507

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tada H., et.al.: "Human betacellulin & member of the EGF family dominantly expressed in pancrease and small intestine is fully active in a monomeric form." Growth Factor. 13. 181-191 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Jinno H., et.al.: "EGF receptor-dependent cytotoxicity for human squamous cell carcinoma cell lines of a conjugate composed of human protein." Life Science. 58. 1901-1908 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Jinno H., et.al.: "EGF receptor-dependent cytotoxic effect by EGF-RNase conjugate on human cancer cell lines." Cancer Chemotherapy and Pharmacology. 38. 303-308 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kaneta Y.,et.al.: "Effects of gelonin conjugate with monoclonal antibody MSN-1 and endometrial adenocarcinoma in vitro" Oncology Report. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Ikeda Y.,et.al.: "Meanings of c-erb B and int-2 oncogene amplification in the patient with superficial esophageal squamous cell carcinomas" Annals of thoracic surgery. 62. 835-858 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Jinno H.,et.al.: "Effect of an adriamycin-immunoconjugate that recognizes the c-erb B-2 product on breast cancer cell lines" Surgery Today. 26. 501-507 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tada H.,et.al.: "Human betacellulin & member of the EGF family dominantly expressed in pancrease and small intestine in fully active in a monomeric form" Growth Factors. 13. 181-191 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Jinno H.,et.al.: "EGF receptor-dependent cytotoxicity for human squamous carcinoma cell lines of a conjugate composed of human proeins" Life Science. 58(21). 1901-1908 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Jinno H.,et.al.: "EGF receptor-dependent cytotoxic effect by EGF-RNase conjugate on human cancer cell lines" Cancer Chemotherapy and Pharmacology. 38(4). 303-308 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Jinno H., et al.: "EGF receptor-dependent cytotoxicity for human squamou carcinoma cell lines of a conjugate composed of human EGF and RNase" Life Sience. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Jinno H., et al.: "EGF receptor-dependent cytotoxic effect by EGF-ribonuclease conjugate on human cancer cell lines." Cancer Chemotherapy and Pharmacology. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Kitagawa Y., et al.: "Further evidence for prognostic significance of EGF receptor gene amplification in patients with esophageal squamous cell carcinoma." Clin. Cancer Res.(in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Jinno H., et al.: "Effect of an adriamycin-immunoconjugate that recognizes the c-erb B-2 product on breast cancer cell lines." Surgery Today. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Kitagawa Y., et al.: "Effect of endogenous and exogenous EGF on the growth of EGF receptor-hyperproducing human squamous cell carcinoma implanted into nude mice" Br. J. Cancer. 72. 865-868 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 上田政和: "DDSの進歩1995-1996" 中山書店, 267 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-03-31   Modified: 2016-04-21  

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