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Experimental Therapy in Mice

Potentiatied antitumor effectiveness of combined chemo-immunotherapy with Interleukin-12 and 5-fluorouracil of L1210 leukemia in vivo

Leukemia volume 15, pages 613–620 (2001)Cite this article

Abstract

In this study we investigated the efficacy of a combination of IL-12 and 5-FU, a chemotherapeutic exerting several immunomodulatory effects, in murine L1210 leukemia. Mice inoculated with 1 × 105 leukemia cells were treated with a single dose of 5-FU (50 mg/kg) and seven daily doses of IL-12 (100 ng/dose), and were observed for survival. Treatment with IL-12 or 5-FU given alone produced moderate anti-leukemic effects. However, combination of both drugs resulted in a significant prolongation of mouse survival time. Importantly, there were 70% of long-term (>60 days) survivors among mice treated with both agents simultaneously. Moreover, we observed 100% of long-term survivors when mice were treated with a minimally increased dose of IL-12 (170 ng) in combination with 5-FU (50 mg/kg). The antileukemic effects were completely abrogated in scid/scid mice and in mice depleted of peritoneal macrophages and significantly decreased after administration of anti-CD3+, anti-CD4+ or anti-CD8+ monoclonal antibodies. Administration of anti-NK1.1 antibodies did not decrease the antileukemic effects indicating that NK cells are not important effectors of this treatment regimen. Collectively, these results indicate that the combination of IL-12 and 5-FU is inducing strong antileukemic responses that are dependent on the presence and activity of macrophages and T lymphocytes and warrant further studies of combined chemo-immunotherapy with IL-12.

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Acknowledgements

This work was supported by the grant No. 4 P05A 071 13 from the State Committee for Scientific Research (KBN) and by ISDS 1M19/S2/2000 from the Medical University of Warsaw.

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  1. J Goła̧b and R Zagożdżon: The first two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Center of Biostructure Research, Medical University of Warsaw, Warsaw, Poland

    J Goła̧b, R Zagożdżon, R Kamiński, K Kozar, T Stokłosa, A Giermasz, W Lasek & M Jakóbisiak

  2. Transplantation Institute, Medical University of Warsaw, Warsaw, Poland

    R Zagożdżon

  3. Department of Cancer Immunology, University School of Medical Sciences, GreatPoland Cancer Center, Poznan, Poland

    K Gryska, D Iżycki & A Mackiewicz

  4. Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA, USA

    R Zagożdżon

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Goła̧b, J., Zagożdżon, R., Kamiński, R. et al. Potentiatied antitumor effectiveness of combined chemo-immunotherapy with Interleukin-12 and 5-fluorouracil of L1210 leukemia in vivo. Leukemia 15, 613–620 (2001). https://doi.org/10.1038/sj.leu.2402076

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