Antitumor effects of interleukin2 against urologic cancer

比较重组白介素2(IL2)和干扰素-γ-GT；(干扰素-γ-GT；)对人肾癌细胞系KU-2、CAKIL和新鲜制备的人肾癌细胞的体外杀伤作用。正常人外周血淋巴细胞在一定浓度范围内与IL-2和干扰素-γ孵育后，用4小时~(51)铬释放法检测细胞毒作用。IL-2增强细胞毒作用具有剂量和时间依赖性。IL-2对肾癌细胞的杀伤作用明显强于干扰素-γ。IL-2的最佳剂量为100~500单位/毫升，即使在低至4单位/毫升的浓度下，细胞毒作用也增加，而且IL-2与干扰素-γ有协同作用。提示全身应用IL-2治疗对干扰素治疗耐药的肾癌是有效的，应考虑持续输注或一天多次给药，以维持较高的血清IL-2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，每次1兆单位，持续4h。1名患者肿瘤显著减少，治疗期间仅有1名患者出现显著进展。治疗后自然杀伤细胞(NK)和淋巴因子激活杀伤细胞(LAK)活性大部分升高，给药方式适合于增强患者的抗肿瘤免疫。未观察到严重不良反应。结果表明，IL-2是一种有效的免疫治疗剂，未来的研究，包括与其他生物反应调节剂的协同作用，可能会为泌尿系癌症的治疗提供新的进展。

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.