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1993 Fiscal Year Final Research Report Summary

The mechanism of interleukin-2 metabolism and its application for the cancer therapy

Research Project

Project/Area Number 03454327
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionKinki University School of Medicine

Principal Investigator

YASUTOMI Masayuki  Kinki University of Medicine Professor, 医学部, 教授 (60028438)

Co-Investigator(Kenkyū-buntansha) SHIGEOKA Hironori  Kinki University of Medicine assistant, 医学部, 助手 (70247998)
OKUNO Kiyotaka  Kinki University of Medicine assistant professor, 医学部, 講師 (30169239)
Project Period (FY) 1991 – 1993
KeywordsInterleukin-2 / IL-2 clearance / Liver metastasis / Liposome / 肝局所免疫 / 肝転移
Research Abstract

We reported previously that interleukin-2 (IL-2) metabolizing enzyme exists in the kidney cytosol. The kidney cytosol fraction was purified using ammonium sulfate precipitation, iron exchange chromatography and IL-2 affinity gel chromatography for obtaining high yields of purfied enzyme. The assay using IL-2 as a substrate of purified fraction showed enzymatic activity to be 64-fold higher than a crude fraction. The Km value of the purified fraction showed approximately 50muM, which means highly specific against IL-2. The SDS-PAGE of the purified fraction showed three bands, 12.3 kDa, 25.7kDa and 61.1kDa, and the 61.1kDa band shows a significant high enzymatic activity. By the immunization of this fraction to a rabbit, polyclonal antibody to IL-2 degradation enzyme was detected in sera. However, the administration of sera never prolonged the serum half-life of IL-2 in mice model.
Another approach for avoiding the short half-life of IL-2, we have tried a chemically modified IL-2 products using liposome. we noticed galactose-receptors existing adundantly in the liver and prepared galactose-containing liposome-IL-2 preparations using various carriers/bases. We infused these preparations in the portal or caudal vein of mice and investigated the accumulation to organs and localized immunological copetence in the liver. As a result, galactose-containing liposome-IL-2 preparations showed the highest accumulation and the highest localized enhancing effect on the antitumor activity of lymphocytes in the liver.

  • Research Products

    (2 results)

All Other

All Publications (2 results)

  • [Publications] Okuno,K.,et al: "Effect of packed red cell and whole blood transfusion on liver-associated immune function.(in press)" Am.j Surg.(1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okuno,K.,et al.: "A successful liver metastasis model in mice with neuraminidase treated colon 26." Surgery Today. 23. 795-799 (1993)

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

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Published: 1995-03-27  

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