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P24. Aviscumine enhances NK- cytotoxicity against tumor cells

  • G Gamerith
  • A Amann
  • B Schenk
  • T Auer
  • JM Huber
  • K Cima
  • H Lentzen
  • J Löffler-Ragg
  • H Zwierzina
  • W Hilbe
Open Access
Poster presentation
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Keywords

Natural Killer Natural Killer Cell Chronic Myelogenous Leukemia Cell Mistletoe Lectin Chromium51 Release Assay 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Background

The mistletoe lectin I belongs to a new class of anticancer drugs with type II ribosomal inhibitor activity. The recombinant mistletoe lectin (aviscumine) has shown immunomodulatory and cytotoxic activity in preclinical models as well as potential antitumor effects in phase I and I/II clinical trials. The aim of this study was to further elucidate the immunostimulatory capacity of aviscumine on natural killer (NK) cell function in a human ex-vivo model.

Methods

The effect of aviscumine (0.5 and 1 ng/ml) on the cellular cytotoxicity of NK cells isolated from peripheral blood mononuclear cells (PBMCs) of 34 healthy volunteers was measured via a standard Chromium51 release assay against K562 chronic myelogenous leukemia cells. For further validation changes in expression of the NK cell activation marker CD107α was determined via flow cytometry (FACS) in 13 volunteers.

Results

Aviscumine induced a significant concentration-dependent increase in NK cellular cytotoxicity in about 54% of the volunteers (p<0.001). This enhancement was also observed with low dose IL-2 stimulation (p=0.01). FACS analysis revealed an aviscumine triggered up-regulation of the NK cell degranulation marker CD107a (p=0.001).

Conclusion

Functional ex-vivo analysis of NK cells from healthy donors revealed a direct immune stimulatory mechanism of aviscumine. These data further strengthen its potential as immunomodulatory antitumor agent and suggest that NK cell activity in peripherial blood may be evaluated as predictive biomarker in clinical trials.

Copyright information

© Gamerith et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors and Affiliations

  • G Gamerith
    • 1
  • A Amann
    • 1
  • B Schenk
    • 2
  • T Auer
    • 3
  • JM Huber
    • 1
  • K Cima
    • 4
  • H Lentzen
    • 5
  • J Löffler-Ragg
    • 4
  • H Zwierzina
    • 1
  • W Hilbe
    • 1
  1. 1.Clinic of Internal Medicine VInnsbruck Medical UniversityInnsbruckAustria
  2. 2.Department of General and Surgical Intensive CareInnsbruck Medical UniversityInnsbruckAustria
  3. 3.Department of RadiologyInnsbruck Medical UniversityInnsbruckAustria
  4. 4.Clinic For Internal Medicine ViInnsbruck Medical UniversityInnsbruckAustria
  5. 5.Cytavis Biopharma GmbhInnsbruckAustria

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