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Local interleukin 2 therapy is most effective against cancer when injected intratumourally

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Abstract

Local interleukin 2 (IL-2) therapy is more effective against systemic tumours than systemic IL-2 therapy, but it remains unclear whether IL-2 should be injected intratumourally or peritumourally. To investigate this question, we treated DBA/2 mice bearing a large subcutaneous syngeneic SL2 lymphoma with either intra or peritumoural IL-2 therapy. Both applications enhanced survival, but intratumourally injected IL-2 was more effective than peritumourally injected IL-2. Tumours started to regress 4 days after IL-2 injection. Tumour cells died at the IL-2 injection site, although IL-2 is not directly cytotoxic for SL2 cells in vitro. Tumour cell death correlated well with oedema and extravascular erythrocytes, but less with leukocyte infiltrates. In mice bearing two s.c. tumours, intratumoural application therapy of IL-2 in one tumour caused decrease in size of both tumours in 4–9 days after therapy. However, the IL-2 treated tumours regressed more strongly than the untreated tumours. We conclude that vascular leakage and/or tissue destruction inside the tumour may contribute to the enhanced effect of intratumoural IL-2 therapy compared to peritumoural IL-2 therapy. Hence, we recommend applying of intratumoural rather than peritumoural IL-2 therapy.

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Acknowledgements

We thank Chiron (Amsterdam) for the kind gift of IL-2.

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Authors and Affiliations

  1. Department of Pathobiology, Faculty of Veterinary Medicine, P.O. Box 80.158, 3508, TD, Utrecht, the Netherlands

    John J. L. Jacobs & Willem Den Otter

  2. Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht, the Netherlands

    John J. L. Jacobs & Derek Sparendam

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  1. John J. L. Jacobs
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Correspondence to John J. L. Jacobs.

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Jacobs, J.J.L., Sparendam, D. & Den Otter, W. Local interleukin 2 therapy is most effective against cancer when injected intratumourally. Cancer Immunol Immunother 54, 647–654 (2005). https://doi.org/10.1007/s00262-004-0627-4

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  • DOI: https://doi.org/10.1007/s00262-004-0627-4

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