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Enhancement of the antibody-dependent cellular cytotoxicity of human peripheral blood lymphocytes with interleukin-2 and interferon α

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Abstract

Antibody-dependent cellular cytotoxicity (ADCC) is regarded as an important mechanism by which monoclonal antibodies (mAb) can exert an antitumour effect in vivo. It may be possible, therefore, to enhance the therapeutic efficacy of mAb by cytokines that are able to enhance the ADCC of human CD3−, CD56+, CD16+ natural killer (NK) cells. We investigated in vitro the effects of recombinant interferon α (rIFNα) and recombinant interleukin 2 (rIL-2), alone or in combination, on the ADCC of human peripheral blood NK cells. Both cytokines enhanced the ADCC of the human effector cells. rIFNα induced a maximally increased ADCC after an exposure of human effector cells to 20 IU/ml for 15–30 min, while rIL-2 induced optimal ADCC after incubation of the cells for 2 days in 20–50 U/ml. We now show that activation of the NK cells with a combination of rIL-2and rIFNα induced significantly higher levels of ADCC than either cytokine alone. The highest ADCC was induced if the cells were first exposed to rIL-2 before rIFNα was added to the culture. Culture of NK cells in medium or rIL-2 decreased the expression of FcγRIII (CD16), indicating that intensity of CD16 expression and level of ADCC are not directly correlated, although blocking experiments with a mAb directed against CD16 showed that this FcγR was essential for ADCC of the human effector cells.

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Author notes

  1. Wim M. J. Vuist

    Present address: Stanford University School of Medicine, Division of Medicine/Oncology, 94 305-5306, Stanford, CA, USA

  2. Marjan J. W. Visseren & Cornelis J. M. Melief

    Present address: Department of Immunohaematology and Bloodbank, Academic Hospital Leiden, Leiden, The Netherlands

Authors and Affiliations

  1. Division of Immunology The Netherlands Cancer Institute, Antoni van Leeuwenhoekhuis, Plesmanlann 121, 1066, CX, Amsterdam, The Netherlands

    Wim M. J. Vuist, Marjan J. W. Visseren, Myrthe Otsen, Karel Bos, Florry A. Vyth-Dreese, Carl G. Figdor, Cornelis J. M. Melief & Annemarie Hekman

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  1. Wim M. J. Vuist
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  2. Marjan J. W. Visseren
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Supported by a grant from the Dutch Cancer Society (grant NKI-84-14)

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Vuist, W.M.J., Visseren, M.J.W., Otsen, M. et al. Enhancement of the antibody-dependent cellular cytotoxicity of human peripheral blood lymphocytes with interleukin-2 and interferon α. Cancer Immunol Immunother 36, 163–170 (1993). https://doi.org/10.1007/BF01741087

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  • DOI: https://doi.org/10.1007/BF01741087

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