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

Laszlo Markasz, Gyorgy Stuber, Bruno Vanherberghen, Emilie Flaberg, Eva Olah, Ennio Carbone, Staffan Eksborg, Eva Klein, Henriette Skribek, Laszlo Szekely

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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.

Original languageEnglish
Pages (from-to)644-654
Number of pages11
JournalMolecular Cancer Therapeutics
Volume6
Issue number2
DOIs
Publication statusPublished - Feb 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Markasz, L., Stuber, G., Vanherberghen, B., Flaberg, E., Olah, E., Carbone, E., Eksborg, S., Klein, E., Skribek, H., & Szekely, L. (2007). Effect of frequently used chemotherapeutic drugs on the cytotoxic activity of human natural killer cells. Molecular Cancer Therapeutics, 6(2), 644-654. https://doi.org/10.1158/1535-7163.MCT-06-0358