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

Abstract

Interleukin(IL)-15, which uses IL-2 receptor (R) β and γ 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-2Rβ+ cells corresponding to natural killer (NK) cells and the production of interferon γ (IFNγ) by T cells in the thoracic exudate cells (TEC). Administration of anti-IFNγ 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.

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Authors and Affiliations

1. Laboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan e-mail: yyoshika@med.nagoya-u.ac.jp Tel.: +81-52-744-2446 Fax: +81-52-744-2449, , , , , , JP
   Keiko Kimura, Hitoshi Nishimura & Yasunobu Yoshikai
2. 1st Department of Surgery, Nagoya University School of Medicine, Nagoya, Japan, , , , , , JP
   Yuji Nimura
3. Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-shi, Tokyo 186, Japan, , , , , , JP
   Takeshi Matsuzaki & Teruo Yokokura

Authors

1. Keiko Kimura
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2. Hitoshi Nishimura
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3. Takeshi Matsuzaki
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4. Teruo Yokokura
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5. Yuji Nimura
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6. Yasunobu Yoshikai
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Received: 13 July 1999 / Accepted: 3 December 1999

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Kimura, K., Nishimura, H., Matsuzaki, T. et al. Synergistic effect of interleukin-15 and interleukin-12 on antitumor activity in a murine malignant pleurisy model.Cancer Immunol Immunother 49, 71–77 (2000). https://doi.org/10.1007/s002620050604

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• Issue Date: April 2000
• DOI: https://doi.org/10.1007/s002620050604