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Granulocyte-monocyte colony-stimulating-factor augments the interleukin-2-induced cytotoxic activity of human lymphocytes in the absence and presence of mouse or chimeric monoclonal antibodies (mAb 17-1A)

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Summary

Blood lymphocytes stimulated for 96 h with interleukin-2 (IL-2; 100 BRMP U/ml) (lymphokine-activated killer, LAK, cells) or granulocyte-monocyte colonystimulating-factor (GM-CSF) (10 ng/ml) became cytotoxic for Daudi cells. IL-2 was significantly more effective than GM-CSF. Only IL-2-activated cells killed SW948 (a human colorectal carcinoma cell line) while GM-CSF-stimulated cell did not. GM-CSF and IL-2 acted synergistically in a dose-dependent fashion for induction of a highly effective cytotoxic cell population (IL-2/GM-CSF cells). Il-2/GM-CSF cells were statistically significantly more effective than LAK cells in lysing Daudi cells and SW948 (P <0.05). The enhancing effect was most pronounced during the first 48–96 h of activation. Incubation periods longer than 192 h did not contribute to augmented cytotoxicity. The combination of IL-2 and GM-CSF significantly increased the number of CD25+ cells compared to IL-2 and GM-CSF alone. Furthermore, IL-2/GM-CSF cells were significantly more effective in antibody-dependent cellular cytotoxicity assays (SW948 + mAb 17-1A) than LAK cells. The chimeric mAb 17-1A was significantly more effective in tumor cell lysis than the mouse mAb. Thus, combination of various biological therapeutics might be a way to enhance their antitumoral effects.

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Authors and Affiliations

  1. Department of Oncology, Radiumhemmet, Immunologic Research Laboratory, Karolinska Hospital, S-10401, Stockholm, Sweden

    Giuseppe Masucci, Peter Ragnhammar, Peter Wersäll & Håkan Mellstedt

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  1. Giuseppe Masucci
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  2. Peter Ragnhammar
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  3. Peter Wersäll
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  4. Håkan Mellstedt
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Masucci, G., Ragnhammar, P., Wersäll, P. et al. Granulocyte-monocyte colony-stimulating-factor augments the interleukin-2-induced cytotoxic activity of human lymphocytes in the absence and presence of mouse or chimeric monoclonal antibodies (mAb 17-1A). Cancer Immunol Immunother 31, 231–235 (1990). https://doi.org/10.1007/BF01789174

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  • DOI: https://doi.org/10.1007/BF01789174

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