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Article

Zoledronic acid negatively affects the expansion of in vitro activated human NK cells and their cytolytic interactions with Ewing sarcoma cells

  • Authors:
    • Sarah-Kristin Mueller
    • Bianca Altvater
    • Christiane Chen
    • Sareetha Kailayangiri
    • Martina Ahlmann
    • Uta Dirksen
    • Heribert Juergens
    • Claudia Rossig
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany
  • Pages: 2348-2354
    |
    Published online on: March 19, 2013
       https://doi.org/10.3892/or.2013.2350
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Abstract

Disseminated Ewing sarcoma remains a fatal disease despite advanced multimodal treatment regimens. Immunotherapies as well as novel drugs and biologicals are currently being explored to eliminate minimal residual disease after conventional therapy thereby rescuing patients at a high risk for relapse. Insights into the interactions between novel therapies provide the basis for the development of effective combination strategies. We investigated the effects of the aminobisphosphonate zoledronic acid (ZA) on the in vitro expansion of human natural killer (NK) cells and their cytolytic activity against Ewing sarcoma cells. ZA significantly impaired the in vitro expansion of activated NK cells from both healthy donors and Ewing sarcoma patients in a dose-dependent manner. Expression of differentiation markers and activating receptors was unaffected by the drug. Activated NK cells from both healthy donors and patients had potent degranulation responses to Ewing sarcoma cells. In the presence of ZA at concentrations reflecting pharmaceutical serum levels, the in vitro antitumor activity of NK cells from Ewing sarcoma patients was significantly impaired. We conclude that ZA can impede in vitro NK cell expansion and cytolytic NK cell responses to Ewing sarcoma. These observations raise caution against the combination of adoptive NK cell transfer with ZA maintenance therapy in Ewing sarcoma. Future studies aim to identify potentiating interactions of novel drugs with cellular therapies.
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Copy and paste a formatted citation
Spandidos Publications style
Mueller S, Altvater B, Chen C, Kailayangiri S, Ahlmann M, Dirksen U, Juergens H and Rossig C: Zoledronic acid negatively affects the expansion of in vitro activated human NK cells and their cytolytic interactions with Ewing sarcoma cells. Oncol Rep 29: 2348-2354, 2013.
APA
Mueller, S., Altvater, B., Chen, C., Kailayangiri, S., Ahlmann, M., Dirksen, U. ... Rossig, C. (2013). Zoledronic acid negatively affects the expansion of in vitro activated human NK cells and their cytolytic interactions with Ewing sarcoma cells. Oncology Reports, 29, 2348-2354. https://doi.org/10.3892/or.2013.2350
MLA
Mueller, S., Altvater, B., Chen, C., Kailayangiri, S., Ahlmann, M., Dirksen, U., Juergens, H., Rossig, C."Zoledronic acid negatively affects the expansion of in vitro activated human NK cells and their cytolytic interactions with Ewing sarcoma cells". Oncology Reports 29.6 (2013): 2348-2354.
Chicago
Mueller, S., Altvater, B., Chen, C., Kailayangiri, S., Ahlmann, M., Dirksen, U., Juergens, H., Rossig, C."Zoledronic acid negatively affects the expansion of in vitro activated human NK cells and their cytolytic interactions with Ewing sarcoma cells". Oncology Reports 29, no. 6 (2013): 2348-2354. https://doi.org/10.3892/or.2013.2350
Copy and paste a formatted citation
x
Spandidos Publications style
Mueller S, Altvater B, Chen C, Kailayangiri S, Ahlmann M, Dirksen U, Juergens H and Rossig C: Zoledronic acid negatively affects the expansion of in vitro activated human NK cells and their cytolytic interactions with Ewing sarcoma cells. Oncol Rep 29: 2348-2354, 2013.
APA
Mueller, S., Altvater, B., Chen, C., Kailayangiri, S., Ahlmann, M., Dirksen, U. ... Rossig, C. (2013). Zoledronic acid negatively affects the expansion of in vitro activated human NK cells and their cytolytic interactions with Ewing sarcoma cells. Oncology Reports, 29, 2348-2354. https://doi.org/10.3892/or.2013.2350
MLA
Mueller, S., Altvater, B., Chen, C., Kailayangiri, S., Ahlmann, M., Dirksen, U., Juergens, H., Rossig, C."Zoledronic acid negatively affects the expansion of in vitro activated human NK cells and their cytolytic interactions with Ewing sarcoma cells". Oncology Reports 29.6 (2013): 2348-2354.
Chicago
Mueller, S., Altvater, B., Chen, C., Kailayangiri, S., Ahlmann, M., Dirksen, U., Juergens, H., Rossig, C."Zoledronic acid negatively affects the expansion of in vitro activated human NK cells and their cytolytic interactions with Ewing sarcoma cells". Oncology Reports 29, no. 6 (2013): 2348-2354. https://doi.org/10.3892/or.2013.2350
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