Lotze M T, Rosenberg S A
Lymphokine Res. 1986;5 Suppl 1:S177-81.
Sequential clinical studies have been conducted over the last seven years in the Surgery Branch, NCI utilizing transferred cells and the administration of interleukin-2 (IL-2). Each study was based on preclinical testing in experimental models or on in vitro evidence suggesting clinical application. Although clinical studies are difficult to conduct as rigorously as those in experimental models, an identical approach is required to obtain meaningful information on which to base subsequent trials. Preclinical testing of lymphokines requires general safety testing in animals, identification of the components with and without biologic activity within the material to be administered, evidence of stability, sterility, lack of pyrogenicity and demonstration of potency. The major clinical goal is to obtain evidence of tumor regression with the added goals of determining other clinical parameters (such as toxicity, half life, endocrine changes and trafficking information). Biologic and immunologic parameters other than those detailed above are routinely obtained to guide further efforts. A sequential evaluation of clinical trials performed in the evaluation of adoptive transfer of activated lymphocytes and the administration of IL-2 is presented.
在过去七年中，国立癌症研究所外科分部利用转移细胞和白细胞介素-2（IL-2）开展了一系列临床研究。每项研究均基于实验模型中的临床前测试或提示临床应用的体外证据。尽管临床研究难以像实验模型中的研究那样严格进行，但仍需要采用相同的方法来获取有意义的信息，以便为后续试验提供依据。淋巴因子的临床前测试需要在动物中进行一般安全性测试，确定待给药材料中具有和不具有生物活性的成分，证明其稳定性、无菌性、无致热原性以及效力。主要临床目标是获得肿瘤消退的证据，并确定其他临床参数（如毒性、半衰期、内分泌变化和转运信息）。除上述详细参数外，还常规获取生物学和免疫学参数以指导进一步研究。本文介绍了在评估活化淋巴细胞的过继转移和IL-2给药时所进行的一系列临床试验评估。
