Protocol design for lymphokine testing in clinical studies of human cancer

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.