| Project/Area Number |
60440093
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OSAWA Toshiaki The University of Tokyo, 薬学部, 教授 (40012603)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI YOSHIRO The University of Tokyo, 薬学部, 助手 (10134610)
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| Project Period (FY) |
1985 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥25,500,000 (Direct Cost: ¥25,500,000)
Fiscal Year 1987: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1986: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1985: ¥21,000,000 (Direct Cost: ¥21,000,000)
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| Keywords | Lymphokine / Monokine / T cell hybridoma / Macrophage hybridoma / Lymphotoxin / Macrophage activating factor / 癌細胞壊死因子 / 殺腫瘍細胞因子 / 抗体産生増強因子 / 殺腫瘍活性 / NK細胞活性化因子 / 腫瘍壊死因子(TNF) |
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| Research Abstract |
1. Lymphokines produced by human T cell hybridomas : We established a novel selection method for the construction of human T cell hybridomas using metabolic inhibitors (emetine and actinomycin D). From one of human T cell hybridoma clones thus established, we cloned cDNA for human lymphotoxin and succeeded to produce a large amounts of recombinant human lymphotoxin. The recombinant human lymphotoxin was found to exert potent cytotoxicity specifically against malignant cells in vitro and in vivo. On the process of the analysis of in vivo anti-tumor activity of human lymphotoxin, we found that human lymphotoxin has potent macrophage chemotactic and macrophage activating activities. From the other human T cell hybridoma clone, H3-E9-6, we partially purified two macrophage activating factors. One of them, MAF-CI, is a priming factor which is not identical with human <gamma>-interferone. The other, MAF-CII, is a triggering factor which is different from lipopolysaccharide. These two macrophage activating factors show a synergistic effect on human monocytes and induce strong tumoricidal activity of human monocytes. Now we are wroking on the complete purification and structural study of these two factors.
2. Monokines produced by human and mouse macrophage hybridomas : We succeeded to establish a number of mouse and human macrophage hybridomas and analyzed various monokines produced by these macrophage hybridomas. One of the human macrophage hybridoma clones established was found to secrete a potent tumor-specific cytotoxin which was distinct from human lymphotoxin, tumor necrosis factor and interleukin-1.
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