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

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.

• Authors: K Kimura, H Nishimura, T Matsuzaki, T Yokokura, Y Nimura, Y Yoshikai
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 49 Issue 2 Pg. 71-7 (May 2000) ISSN: 0340-7004 [Print] Germany
• PMID: 10823416 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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)