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Clinical and immunological effects of human recombinant interleukin-2 given by repetitive weekly infusion to normal dogs

  • Original Articles
  • Canine, Cytotoxicity, Interleukin-2, In Vivo, Infusion, Lymphocyte
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Four normal adult dogs received two consecutive weekly cycles of human recombinant interleukin-2 (IL-2) by continuous infusion for 4 days/week. The dose of IL-2 given to each dog was 3×106 units m−2 day−1. Toxicities consisted of mild vomiting, diarrhea, and lethargy to varying degrees in all the dogs. These side-effects were reversed when the treatment was discontinued. Fever, tachypnea, and weight gain were not seen. A marked lymphocytosis and eosinophilia developed in all dogs after completion of each course of IL-2 (resulting in a more than sevenfold increase in each cell type) and persisted for more than 1 month in some. Fresh peripheral blood lymphocytes (PBL) obtained during this lymphocytosis mediated enhanced in vitro lysis of a natural-killer-cell-sensitive canine tumor cell line (CTAC). The in vitro proliferative responses of these same PBL to IL-2 could be detected earlier, progressed faster, and involved more cells than PBL tested prior to IL-2 infusion. Thus, a relatively well-tolerated regime of IL-2 in dogs can induce dramatic increases in lymphocyte numbers and activation, which is associated with augmentation of their in vitro antitumor reactivity. The clinical effectiveness of this immunotherapeutic approach remains to be tested in tumor-bearing dogs where it could serve as a relevant large-animal model for immunotherapy of cancer with IL-2.

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Authors and Affiliations

  1. Department of Medical Sciences, University of Wisconsin-Madison, USA

    Stuart C. Helfand & Steve A. Soergel

  2. Department of Pathobiological Sciences, University of Wisconsin-Madison, USA

    Peter S. MacWilliams

  3. Department of Human Oncology, University of Wisconsin-Madison, USA

    Jacquelyn A. Hank & Paul M. Sondel

  4. Department of Pediatrics, University of Wisconsin-Madison, USA

    Paul M. Sondel

  5. Department of Genetics, University of Wisconsin-Madison, USA

    Paul M. Sondel

  6. School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive West, 53706, Madison, WI, USA

    Stuart C. Helfand, Steve A. Soergel & Peter S. MacWilliams

  7. School of Medicine, University of Wisconsin-Madison, USA

    Jacquelyn A. Hank & Paul M. Sondel

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  1. Stuart C. Helfand
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  2. Steve A. Soergel
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Additional information

This work was supported by grants from the University of Wisconsin Graduate School. University of Wisconsin School of Veterinary Medicine Companion Animal Fund, NIH CA-32685, CM-87290, and American Cancer Society CH-237

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Helfand, S.C., Soergel, S.A., MacWilliams, P.S. et al. Clinical and immunological effects of human recombinant interleukin-2 given by repetitive weekly infusion to normal dogs. Cancer Immunol Immunother 39, 84–92 (1994). https://doi.org/10.1007/BF01525313

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  • DOI: https://doi.org/10.1007/BF01525313

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