Antitumor effects of interleukin2 against urologic cancer

白细胞介素2对泌尿系统癌症的抗肿瘤作用

• 批准号: 60570758
• 负责人: BABA Shiro
• 金额: $ 1.09万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60570758/
• 关键词: Interleukin2; Urologic cancer; Renal cell carcinoma; 免疫療法

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.

比较了重组白细胞介素2（IL 2）和干扰素<gamma>（IFN-γ<gamma>）对淋巴细胞介导的杀伤人肾癌细胞KU-2、Cakil及新鲜制备的人肾癌细胞的作用。正常成人外周血淋巴细胞与不同浓度的IL-2和IFN-γ孵育后<gamma>，用4 hr ~（51）Cr释放法测定细胞毒性。IL-2的细胞毒性增强是剂量和时间依赖性的。IL-2对肾癌细胞的杀伤作用明显强于IFN-γ<gamma>。IL-2的最适剂量为100 ~ 500 units/ml，即使浓度低至4units/ml，细胞毒性也增加。IL-2和IFN-γ具有<gamma>协同作用。结果表明，全身给予IL-2对治疗对干扰素治疗耐药的肾细胞癌有效，应考虑连续输注或一天内多次重复给药，以维持血清中IL-2的高水平。在基础实验结果的基础上，对7例晚期肾癌患者静脉滴注IL-2，剂量为100万单位，持续4小时。在一名患者中观察到显著的肿瘤缩小，并且在治疗期间仅在一名患者中观察到显著的进展。大多数患者的自然杀伤细胞（NK）活性和淋巴因子激活的杀伤细胞（LAK）活性升高，表明给药方式适合于增强患者的抗肿瘤免疫力。未观察到严重不良反应。结果表明，IL-2是一种有效的免疫调节剂，未来的研究，包括与其他生物反应调节剂的协同作用，可能会在泌尿系癌症的治疗中取得进展。

项目成果

上野宗久: Keio J Med. 35. 80-89 (1986)

上野宗久：庆应义塾医学杂志 35. 80-89 (1986)

Ueno,Munehisa: "Interleukin 2 induced cytotoxicity on renal cell carcinoma, 2.Synergistic effects of interleukin 2 and interferon gamma" Keio J Med. 35. 90-100 (1986)

Ueno，Munehisa：“白细胞介素 2 诱导肾细胞癌的细胞毒性，2.白细胞介素 2 和干扰素 γ 的协同作用”Keio J Med。

上野宗久: Keio J Med. 35. 90-100 (1986)

上野宗久：庆应义塾医学杂志 35. 90-100 (1986)

Ueno,Munehisa: "Interleukin 2 induced cytotoxicity on renal cell carcinoma, 1.In vitro enhancement of natural killer cell activity" Keio J Med. 35. 80-89 (1986)

Ueno，Munehisa：“白细胞介素2诱导肾细胞癌的细胞毒性，1.自然杀伤细胞活性的体外增强”Keio J Med。