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

P. Lissoni, S. Barni, M. Mandalá, F. Rovelli, G. Cangemi, L. Fumagalli, D. Pirato, L. Vigoré, M. G. Roselli, G. Tancini, M. G. Viganó, L. Giani

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)41-44
Number of pages4
JournalInternational Journal of Immunotherapy
Volume14
Issue number1
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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