IMMUNOTHERAPY BY A SLOW DELIVERY SYSTEM OF INTERLEUKIN-2 IN MICE MODELS

A sustained release system for interleukin-2 (IL-2), and IL-2 mini-pel let (IL-2 mp), was developed by fusing IL-2 into a needle shaped colla gen. Serum concentration of IL-2 after a single subcutaneous injection of the IL-2 mp into C57BL/6 mice remained elevated longer than after an injection of aqueous IL-2. IL-2 in the serum became undetectable by 6h after a subcutaneous injection of 1 X 10(6) unit of IL-2 in phosph ate-buffered saline (PBS). In contrast, after a single subcutaneous in jection of IL-2 mp containing the same amount of IL-2, the concentrati on of IL-2 increased to its maximum at 6h after injection, then began to decrease gradually. IL-2 was detected even on the third day after a single subcutaneous injection of one IL-2 mp. Augmentation of NK acti vity and generation of IL-2 activated killer cells were observed in th e spleen from day 1 - day 3 after a single subcutaneous injection of I L-2 mp into C57BL/6 mice. This activation was not observed following a single subcutaneous injection of the same amount of IL-2 in PBS. Adop tive immunotherapy by a single subcutaneous injection of IL-2 mp follo wed by intravenous injections of in vitro cultured IL-2 activated kill er cells showed better results in decreasing the number of metastases of Lewis lung carcinoma in C57BL/6 mice than immunotherapy using IL-2 solution. This slow delivery system of IL-2 appears promising in the a pplication of adoptive immunotherapy now under investigation in human subjects because it augments biological effects by prolonging the dura tion of interaction of IL-2 and its receptive cells and decreases side effects by lowering maximal concentrations.