Immunobiological effects of interleukin-2, interleukin-12 or interleukin-2 plus interleukin-12 in metastatic cancer patients

IL-2 and IL-12 seem to be the main antitumor cytokines in humans. IL-2 induced tumor regression is associated with important lymphocytosis. In contrast, lymphocyte number lends to decrease in response to IL-12, and this evidence could reduce in vivo its potential anticancer activity. This preliminary biological study was performed to evaluate the in vivo influence of IL-2 on IL-12-induced lymphocyte decline. The study was carried out in metastatic renal cell cancer patients, who underwent 1-week courses of subcutaneous (SC) IL-2 alone; IL-12 alone; or IL-12 plus IL-2. Six courses consisted of IL-2 plus IL-12; the results were compared with those observed during 12 courses with IL-2 alone, and 12 courses with IL-12 alone. IL-2 was given at 3 million IU/day in the evening every day for 6 days. IL-12 was injected at 0.5 mcg/kg in the morning once/week. During their association, IL-12 was injected 3 days prior to IL-2. Lymphocyte mean number increased on low-dose IL-2 alone, without significant differences with respect to the baseline values. Mean number of lymphocytes significantly decreased after IL-12 alone. In contrast, a very significant increase in lymphocyte mean number occurred in response to IL-12 plus IL-2. In addition, the increase in mean serum levels of both neopterin and sIL-2R achieved during the immunotherapy with IL-12 plus IL-2 was significantly higher than in response to IL-2 alone or IL-12 alone. In conclusion, this preliminary study seems to suggest that the concomitant injection of IL-12 and IL-2 may abrogate IL-12-induced lymphocytopenia and amplify the immunomodulatory effects of both IL-2 and IL-12. Therefore, at least from an immunobiological point of view, the immunotherapy of cancer with IL-12 plus IL-2 could represent one of the most promising future cytokine combinations in the treatment of human neoplasms.