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Research Articles: Therapeutics, Targets, and Development

Effect of frequently used chemotherapeutic drugs on the cytotoxic activity of human natural killer cells

¹ Department of Microbiology, Tumor and Cell Biology (MTC) and Center for Integrative Recognition in the Immune System, Karolinska Institute; ² Karolinska Pharmacy and Department of Woman and Child Health, Childhood Cancer Research Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; ³ Department of Pediatrics, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary; and ⁴ Department of Experimental and Clinical Medicine "G Salvatore," University "Magna Graecia," Catanzaro, Italy

Requests for reprints: Laszlo Szekely, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Box 280, SE-171 77 Stockholm, Sweden. Phone: 46-8-524-86760; Fax: 46-8-330-498. E-mail: lassze{at}ki.se

Abstract

Tumors are considered to be possible targets of immunotherapy using stimulated and expanded autologous or allogeneic natural killer (NK) cells mismatched for MHC class I molecules and inhibitory NK receptors. NK cell–based immunoadjuvant therapies are carried out in combination with standard chemotherapeutic protocols. In the presented study, we characterized the effect of 28 frequently used chemotherapeutic agents on the capacity of NK cells to kill target cells. We found that treatment of NK cells with the drugs vinblastine, paclitaxel, docetaxel, cladribine, chlorambucil, bortezomib, and MG-132 effectively inhibited NK cell–mediated killing without affecting the viability of NK cells. On the other hand, the following drugs permitted efficient NK cell–mediated killing even at concentrations comparable with or higher than the maximally achieved therapeutic concentration in vivo in humans: asparaginase, bevacizumab, bleomycin, doxorubicin, epirubicin, etoposide, 5-fluorouracil, hydroxyurea, streptozocin, and 6-mercaptopurine. [Mol Cancer Ther 2007;6(2):644–54]

Grant support: The Swedish Cancer Society, the Swedish Research Council, and the Integrative Recognition in the Immune System Center.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: L. Markasz and G. Stuber contributed equally to this work.

⁵ GlaxoSmithKline Research Triangle Park N. Prescribing Information Leukeran. Available from: http://us.gsk.com/products/assets/us_leukeran.pdf.

Received 6/21/06; revised 11/14/06; accepted 12/22/06.

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