In this project, we have studied in-vivo generation of LAK, NK, and CTL activities in response to IL-2 and IFN-alpha administration in the organs of mice. The data indicate that administration of IL-2 for 3 consecutive days is capable of generating LAK activity and enhance NK mediated cytotoxicity from splenic and hepatic lymphocytes. Administration of a mixture of IFN-alpha and IL-2 enhanced LAK activity compared to group treated with IL- alone. In both spleen and liver cells, LAK activity was enhanced. The induction of NK activity was also observed by IFN-alpha and IL-2 administration but the results were variable. Continued administration of IFN-alpha and IL-2 for 7 days caused synergistic augmentation of LAK activity in both liver and spleen cells. IL-2 administration alone caused generation of LAK but activity was lower than observed after 3 days of therapy. These studies indicate that potent LAK or 'super LAK' cells are generated by IL-2 and IFN-alpha-therapy in vivo and this may explain, at least in part, the synergistic anti-tumor effects of this combination therapy in mouse as well as in man. We have also analysed the phenotype of proliferating cells in the spleens and livers of mice from various treatmen groups. IL-2 administration caused an increase in the percentage Thy 1.2 an Asialo-GM-1 positive cells in both organs. The administration of both IL-2 and IFN-alpha also increased Thy 1.2 and Asialo-GM-1 positive cells and thi increase in the liver appeared to be greater than caused by IL-2 alone. The CTL response is currently being investigated.
