1993 Fiscal Year Final Research Report Summary
The mechanism of interleukin-2 metabolism and its application for the cancer therapy
| Project/Area Number |
03454327
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Kinki University School of Medicine |
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Principal Investigator |
YASUTOMI Masayuki Kinki University of Medicine Professor, 医学部, 教授 (60028438)
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| 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)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Interleukin-2 / IL-2 clearance / Liver metastasis / Liposome / 肝局所免疫 / 肝転移 |
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| 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.
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