| Project/Area Number |
60570758
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | Keio University |
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Principal Investigator |
BABA Shiro (1986) School of Medicine,Keio University, 医学部, 講師 (00051889)
丸茂 健 (1985) 慶応義塾大学, 医学部, 助手
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| Co-Investigator(Kenkyū-buntansha) |
OUHASHI Masakazu School of Medicine,Keio University, 医学部, 助手 (50169041)
UENO Munehisa School of Medicine,Keio University, 医学部, 助手 (60167286)
MARUMO Ken School of Medicine,Keio University, 医学部, 非常勤講師 (80138130)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Interleukin2 / Urologic cancer / Renal cell carcinoma / 免疫療法 |
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| Research Abstract |
The effects of recombinant interleukin2(IL2) and inteferon- <gamma> (IFN- <gamma> ) on lymphocyte-mediated cytotoxicity against human renal carcinoma cell line KU-2 and Cakil,and freshly prepared human renal carcinoma cells were compared in vitro. After incubation of peripheral blood lymphocytes from normal adult volunteers with IL-2 and IFN- <gamma> , over a range of concentrations,cytotoxicity was determined by 4hr 51Cr-release assay. Augmentation of cytotoxicity by IL-2 was dose- and time-dependent. IL-2 induced significantly greater cytotoxicity against renal carcinoma cells than did IFN- <gamma> . The optomal dose of IL-2 was 100 to 500units/ml,and cytotoxicity increased even at concentration as low as 4units/ml. Furthermore,it was demonstrated that IL-2 and IFN- <gamma> have synergistic effects. The results indicated that the systemic administration of IL-2 to patients will effective for treatment of renal cell carcinoma which is resistant to IFN therapy,and continuous infusion or multiple repeated doses over the period of a day should be considered in order to maintain high level of IL-2 in the serum. Based on obtained results of basic experiments,IL-2 was administered to 7 patients with advanced renal cell carcinoma by intravenous drip infusion over 4 hour period at a dose of 1mega units. Significant tumor reduction was observed in one patient and significant progression during the therapy was observed in only one patient. Natural killer(NK) activity and lymphokine-activated killer(LAK) activity increased in the most of patients treated,and mode of administration was demonstrated to be suitable to augment anti-tumor immunity of the patients. No serious adverse effects was obseved. Results indicated that IL-2 is a potent immunotherapeutic agent,and future studies,including synergistic effects with other biological response modifiers,may provide progress in treatment of urologic cancer.
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