INVIVO ADMINISTRATION OF PURIFIED JURKAT-DERIVED INTERLEUKIN-2 IN MICE

Abstract

Pure human inerleukin 2 (IL-2), produced by the T-cell lymphoma Jurkat, was injected in mice to study the serum half-life (t1/2), toxicity, and in vivo immunological effects of IL-2. The serum half-life of Jurkat IL-2 in mice appeared to have 2 components: a rapid intial phase with t1/2 of .apprx. 2 min during which most of the exogenous IL-2 was cleared from the serum; and a 2nd, slower component with t1/2 of about 9 min. Mice given injections i.p. or i.v. with pure Jurkat IL-2, at doses comparable on a .mu.q/kg basis to contemplated doses for humans, showed no signs of toxicity on the basis of serial measurements of weight, serum liver and kidney chemistries, or histology of lymphoid and vital organs. Jurkat IL-2 had no effect on the rate of growth or survival of mice with established s.c. methylcholanthrene-induced fibrosarcoma [mouse MCA-102 cells], but Jurkat IL-2 used in conjunction with in vitro-resensitized and IL-2-expanded specific immune splenocytes prolonged survival of mice with disseminated FBL-3 tumor [mouse lymphoma]. This survival prolongation was highly significant when compared to treatment with Jurkat IL-2 alone (P = < 0.001) or an equivalent number of in vitro-resensitized and expanded cells alone (P = 0.004). Treatment of mice with i.p. Jurkat IL-2 subsequent to secondary immunization with allogeneic tumor enhanced by more than 5-fold the splenocyte cytotoxicity for alloantigen measured 7 days later. Thus, purified human IL-2 derived from the Jurkat cell line has a short half-life in mice with no apparent toxicity at large doses. In vivo efficacy of human IL-2 was demonstrated in increasing alloantigen responsiveness and in increasing the efficacy of transferred expanded immune lymphocytes in the FBL-3 lymphoma model.