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 tends to decrease in response to IL-12, and this evidence could reduce in vivo its potential anticancer activ ity. This preliminary biological study was performed to evaluate the i n vivo influence of IL-2 on IL-12-induced lymphocyte decline. The stud y was carried out in metastatic renal cell cancer patients, who underw ent 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 w ere compared with whose observed during 12 courses with IL-2 alone, an d 12 courses with IL-12 alone. IL-2 was given at 3 million IU/day in t he evening every day for 6 days, IL-12 was injected at 0.5 mcg/kg in t he morning once/week. During their association, IL-12 was injected 3 d ays prior to IL-2. Lymphocyte mean number increased on low-dose IL-2 a lone, without significant differences with respect to the baseline val ues. Mean number of lymphocytes significantly decreased after IL-12 lo ne. 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 im munotherapy with IL-12 plus IL-2 was significantly higher than in resp onse to IL-2 alone or IL-12 alone. In conclusion, this preliminary stu dy seems to suggest that the concomitant injection of IL-12 and IL-2 m ay abrogate IL-12-induced lymphocytopenia and amplify the immunomodula tory effects of both IL-2 and IL-12. Therefore, at least from an immun obiological point of view, the immunotherapy of cancer with IL-12 plus IL-2 could represent one of the most promising future cytokine combin ations in the treatment of human neoplasms.