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Further development of local IL-2 therapy of cancer: multiple versus single IL-2 treatment of transplanted murine colon carcinoma

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Abstract

We have compared the effect of one and up to four local IL-2 treatments of transplanted MC38 colon carcinoma. A single IL-2 treatment prolonged the survival time (p=0.015), but no cure was obtained. One local IL-2 treatment inhibited tumor growth for about 1 week. After the start of tumor regrowth, a further IL-2 injection was given. After four IL-2 injections 6 out of 13 mice were cured. Histological studies show that IL-2 induced a local vascular leakage syndrome leading to massive peritumoral edema and subsequent necrosis of tumor tissue. IL-2 also attracted infiltrating cells, mainly macrophages. Subsequent IL-2 injections led to complete tumor regression. We believe that the combination of necrotic tumor debris and the IL-2–induced macrophage reaction enhanced a tumor-specific immune response. This local IL-2 application was not toxic.

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Acknowledgements

These studies were partly supported by grants from the Agreement between the Polish Academy of Sciences and the Royal Dutch Academy of Sciences, and by grant no. 4 PO5A 123 14 from the Committee for Scientific Research of the Republic of Poland. IL-2 was a kind gift from Chiron, Amsterdam. Photomicrographs were made in the Center for Cell Imaging (Dept. of Biochemistry, Cell Biology and Histology, Faculty of Veterinary Medicine, University of Utrecht).

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Authors and Affiliations

  1. Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla St. 12, 53-114, Warsaw, Poland

    Halina Kusnierczyk & Elzbieta Pajtasz-Piasecka

  2. Department of Cell Biology and Histology, PO Box 80.176, 3508 TD, Utrecht, The Netherlands

    Jan-Willem Koten, Caspaar Bijleveld & Willem Den Otter

  3. Department of Veterinary Pathology, Utrecht, The Netherlands

    Willem Den Otter

  4. Institute of Molecular Biology, Jagiellonian University, 3 Mickiewicz Ave., 31-120, Krakow, Poland

    Krzysztof Krawczyk

Authors
  1. Halina Kusnierczyk
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  2. Elzbieta Pajtasz-Piasecka
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  3. Jan-Willem Koten
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  4. Caspaar Bijleveld
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  5. Krzysztof Krawczyk
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  6. Willem Den Otter
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Correspondence to Willem Den Otter.

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Kusnierczyk, H., Pajtasz-Piasecka, E., Koten, JW. et al. Further development of local IL-2 therapy of cancer: multiple versus single IL-2 treatment of transplanted murine colon carcinoma. Cancer Immunol Immunother 53, 445–452 (2004). https://doi.org/10.1007/s00262-003-0490-8

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  • DOI: https://doi.org/10.1007/s00262-003-0490-8

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