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Local interleukin-2 therapy in bovine ocular squamous cell carcinoma

A pilot study

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Summary

Five cows bearing bovine ocular squamous cell carcinoma (BOSCC) were treated with low doses of recombinant human interleukin-2 (rhIL-2). A dose of 2500 U rhIL-2 was injected intralesionally and another 2500 U were injected into the subparotid regional lymph node once a day during a period of 5 consecutive days. This cycle of 5 days was repeated after an interval of 2 days. Total regression of the tumor was observed in three out of five animals. One cow showed tumor regression (> 80%) accompanied by metastases to the regional lymph node that were observed from the fifth week after the beginning of the treatment. Growth of the tumor of the fifth animal was retarded after treatment. In vitro proliferation of peripheral blood lymphocytes was investigated in two animals and tumor-infiltrating lymphocytes in one animal during incubation in various rhIL-2 concentrations. Cytotoxic activity of both cell populations against P815, Yac-1 and BOSCC-derived cell lines increased during incubation with rhIL-2. Cultured BOSCC-infiltrating lymphocytes showed predominant killing of the BOSCC-derived autologous cell line after 4 weeks of culture. Preliminary phenotype analysis did not give conclusive results with respect to the types of cells responsible for killing.

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References

  1. Baldwin CL, Teale AJ, Naessens JG, Goddeeris BM, MacHugh ND, Morrison I (1986) Characterization of a subset of bovine T lymphocytes that express BoT4 by monoclonal antibodies and function: similarity to lymphocytes defined by human T4 and murine L3T4. J Immunol 136: 4385–4391

    Google Scholar 

  2. Bubenik J, Perlmann P, Indrova M, Simova J, Jandlova T, Neuwirt J (1983) Growth inhibition of an MC-induced mouse sarcoma by TCGF (IL2)-containing preparations. Preliminary report. Cancer Immunol Immunother 14: 205–206

    Google Scholar 

  3. Bubenik J, Indrova M, Perlmann P, Berzins K, Mach O, Kraml J, Toulcova A (1985) Tumour inhibitory effects of TCGF/IL2 containing preparations. Cancer Immunol Immunother 19: 57–61

    Google Scholar 

  4. Bubenik J, Indrova M (1987) Cancer immunotherapy using local interleukin-2 administration. Immunol Lett 16: 305–310

    Google Scholar 

  5. Cook CG, Splitter GA (1988) Lytic function of bovine lymphokine activated killer cells from a normal and a malignant catharral fever virus-infected animal. Vet Immunol Immunopathol 19: 105–118

    Google Scholar 

  6. Darrow TL, Slingluff CL, Seigler HF (1988) Autologous lymph node cell-derived tumor-specific cytotoxic T-cells for use in adoptive immunotherapy of human melanoma. Cancer 62: 84–91

    Google Scholar 

  7. Davis WC, Ellis JA, MacHugh ND, Baldwin CL (1988) Bovine pan T-cell monoclonal antibodies reactive with a molecule similar to CD2. Immunology 63: 165–167

    Google Scholar 

  8. Ellis JA, Baldwin CL, MacHugh ND, Bensaid A, Teale AJ, Goddeeris BM, Morrison WI (1988) Characterization by a monoclonal antibody and functional analysis of a subset of bovine T lymphocytes that express BoT8, a molecule analogous to human CD8. Immunology 58: 351–358

    Google Scholar 

  9. Fenwick BW, Schore CE, Osburn BI (1988). Human recombinant IL2.125 induced in vitro proliferation of equine, caprine, ovine, canine and feline peripheral blood lymphocytes. Comp Immunol Microbiol Infect Dis 11: 51–60

    Google Scholar 

  10. Fong S, Doyle MV (1986) Response of bovine and porcine peripheral blood mononuclear cells to human recombinant interleukin-2.125. Vet Immunol Immunopathol 11: 91–100

    Google Scholar 

  11. Forni G (1987) Immunotherapy. Local application of interleukin-2. Proceedings of the European Course on Clinical Tumor Immunology, Zeist, The Netherlands, 7–10 Dec

  12. Forni G, Giovarelli M (1987) Tumor immunotherapy with interleukin-2 and leukocytes. Research Monographs in Immunology 11, 279–281

    Google Scholar 

  13. Glauser FL, DeBlois GG, Bechard DE, Merchant RE, Grant AJ, Fowler AA, Fairman RP (1988) A comparison of the cardiopulmonary effects of continuous versus bolus infusion of recombinant interleukin-2 in sheep. Cancer Res 48: 2221–2225

    Google Scholar 

  14. Klein WR, Steerenberg PA, Poelma F, Van der Wiel E, Rutten VPMG, Misdorp W, De Jong WH, Ruitenberg EJ (1986) Immune reactivity in cattle with ocular squamous cell carcinoma after intralesional BCG immunotherapy. Cancer Immunol Immunother 22: 87–94

    Google Scholar 

  15. Lafreniere R, Rosenberg SA (1985) Successful immunotherapy of murine experimental hepatic metastases with lymphokine-activated killer cells and recombinant interleukin-2. Cancer Res 45, 3735–3741

    Google Scholar 

  16. Mazumder A, Rosenberg SA (1984) Successful immunotherapy of natural killer resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin-2. J Exp Med 159: 495–597

    Google Scholar 

  17. Pizza C, Severini G, Menniti D, De Vinci C, Corrado F (1984) Tumour regression after intralesional injection of interleukin-2 (IL-2) in bladder cancer. Int J Cancer 34: 367–395

    Google Scholar 

  18. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SF, Matory YL, Skibber JM, Shiloni E, Vetto JT, Seipp CA, Simpson C, Reichert CM (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313: 1485–1492

    Google Scholar 

  19. Rosenberg SA, Mule JJ, Spiess PJ, Reichert CM, Schwarz SL (1985) Regression of established pulmonary and subcutaneous tumor mediated by systemic administration of recombinant interleukin-2. J Exp Med 161: 1169–1188

    Google Scholar 

  20. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT, Seipp CA, Simpson C, Reichert CM (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high dose interleukin-2 alone. N Engl J Med 316: 889–897

    Google Scholar 

  21. Sondel PM, Kohler PC, Hank JA, Moore KH, Rosenthal NS, Sosman JA, Bechhofer R, Storer B (1988) Clinical and immunological effects of recombinant interleukin-2 given by repetitive weekly cycles to patients with cancer. Cancer Res 48: 2561–2567

    Google Scholar 

  22. Stott JL, Fenwick BW, Osburn BI (1986) Human recombinant interleukin-2 augments in vitro blastogenesis of bovine and porcine lymphocytes. Vet Immunol Immunopathol 13: 31–38

    Google Scholar 

  23. Talmadge JE, Philips H, Schindler J, Tribble H, Pennington R (1987) Systemic preclinical study on the therapeutic properties of recombinant human interleukin 2 for the treatment of metastatic disease. Cancer Res 47: 5725–5732

    Google Scholar 

  24. Vaage J (1987) Local and systemic effects during interleukin-2 therapy of mouse mammary tumors. Cancer Res 47: 4295–4296

    Google Scholar 

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Authors and Affiliations

  1. Department of Immunology, Faculty of Veterinary Medicine, State University of Utrecht, P. O. Box 80.165, 3508 TD, Utrecht, The Netherlands

    V. P. M. G. Rutten, W. A. C. De Jong & E. J. Ruitenberg

  2. Department of Surgery, Faculty of Veterinary Medicine, State University of Utrecht, The Netherlands

    W. R. Klein

  3. Department of Pathology, Faculty of Veterinary Medicine, State University of Utrecht, and The Netherlands Cancer Institute, Amsterdam, The Netherlands

    W. Misdorp

  4. Pathological Institute, Faculty of Medicine, State University of Utrecht, The Netherlands

    W. Den Otter

  5. RIVM, Bilthoven, The Netherlands

    W. Den Otter, P. A. Steerenberg, W. H. De Jong & E. J. Ruitenberg

Authors
  1. V. P. M. G. Rutten
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  2. W. R. Klein
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  3. W. A. C. De Jong
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  4. W. Misdorp
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  5. W. Den Otter
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  6. P. A. Steerenberg
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  7. W. H. De Jong
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  8. E. J. Ruitenberg
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Rutten, V.P.M.G., Klein, W.R., De Jong, W.A.C. et al. Local interleukin-2 therapy in bovine ocular squamous cell carcinoma. Cancer Immunol Immunother 30, 165–169 (1989). https://doi.org/10.1007/BF01669425

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  • DOI: https://doi.org/10.1007/BF01669425

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