Synergistic effect of interleukin-15 and interleukin-12 on antitumor activity in a murine malignant pleurisy model

Cancer Immunol Immunother. 2000 May;49(2):71-7. doi: 10.1007/s002620050604.

Abstract

Interleukin(IL)-15, which uses IL-2 receptor (R) beta and gamma chains for signal transduction, shares many of the biological activities of IL-2. We examined the effects of exogenous IL-15 on protection in a murine malignant pleurisy model using BALB/c mice and syngeneic MethA fibrosarcoma (MethA). Intrapleural administration of IL-15 significantly prolonged the survival time of mice after an intrapleural inoculation of MethA, whereas the same dose of IL-2 did not. The in vivo antitumor effect of IL-15 was synergistically enhanced by additive administration of IL-12. Combination therapy of IL-15 and IL-12 protected mice from death from bloody pleural fluid. Such treatment induced marked increases in the number of CD3-IL-2Rbeta+ cells corresponding to natural killer (NK) cells and the production of interferon gamma (IFNgamma) by T cells in the thoracic exudate cells (TEC). Administration of anti-IFNgamma mAb partly inhibited the protective effect of a combination of IL-15 and IL-12. A tumor-neutralizing (Winn) assay revealed that the antitumor activity of effector cells in the TEC was abrogated by treatment with anti-CD8 mAb or anti-asialoGM1 Ab plus complement. Thus, treatment with IL-15 in combination with IL-12 may enhance the activities of NK and CD8+ T cells in the TEC, providing strong antitumor activity against the malignant pleurisy. These results suggest that IL-15 together with IL-12 may have potential for the immunotherapy of some types of malignant pleurisy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Synergism
  • Fibrosarcoma / drug therapy*
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / administration & dosage*
  • Interleukin-15 / administration & dosage*
  • Killer Cells, Natural / drug effects
  • Male
  • Methylcholanthrene
  • Mice
  • Mice, Inbred BALB C
  • Pleurisy / drug therapy*
  • Rats
  • Recombinant Proteins / therapeutic use

Substances

  • Interleukin-15
  • Recombinant Proteins
  • Interleukin-12
  • Methylcholanthrene
  • Interferon-gamma