Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells

  • Authors:
    • Gabriele Gamerith
    • Arno Amann
    • Bettina Schenk
    • Thomas Auer
    • Hans Lentzen
    • Dirk O. Mügge
    • Katharina M. Cima
    • Judith Löffler‑Ragg
    • Wolfgang Hilbe
    • Heinz Zwierzina
  • View Affiliations

  • Published online on: August 31, 2017     https://doi.org/10.3892/ol.2017.6861
  • Pages: 5563-5568
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Abstract

Aviscumine, a recombinant lectin I, has been identified as an immunomodulatory agent within a new class of ribotoxic stress‑inducing anticancer substances that have demonstrated efficacy in phase I/II trials. The aim of the present study was to elucidate the presumed effect of aviscumine on enhancing human natural killer (NK) cell antitumor cytotoxicity. To measure the effect of aviscumine on human NK cell cytotoxicity, chromium‑51‑release assays against K‑562 cells were performed with isolated NK cells from the whole blood of 34 healthy volunteers. Two effector‑to‑target cell ratios (12.5:1 and 25:1) were used by two independent investigators with a focus on the concentration‑dependent effect (0.5 vs. 1 ng/ml aviscumine), reproducibility (first vs. second investigator) and the specificity of the effect by comparison to a heat‑inactivated aliquot and interleukin 2 (IL‑2) stimulation (10 ng/ml). The mediation of the effect via degranulation was demonstrated by flow cytometric analyses of CD107α expression. Statistics were performed with SPSS using Student's t‑tests for normally distributed data. Aviscumine induced a significant and reproducible, concentration‑dependent increase in NK cell cytotoxicity (n=22; P<0.01 for both concentrations and ratios), which was also demonstrated when administered in combination with IL‑2 (n=12; 12.5:1 ratio, P<0.001; 25:1 ratio, P=0.025) and when compared with the heat‑inactivated aliquots (n=12; 12.5:1, P=0.004; 25:1 ratio, P=0.007). The mediation of its effect via interferon γ degranulation was demonstrated by significantly enhanced CD107α expression (n=7; P=0.005). Taken together, the results indicate that aviscumine induced an increase in NK cell anticancer cytotoxicity. These results highlight its clinical potential as an immunostimulatory agent, particularly with regard to combined use with chemotherapeutics or immune checkpoint inhibitors. However, further studies are required.
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November-2017
Volume 14 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Gamerith G, Amann A, Schenk B, Auer T, Lentzen H, Mügge DO, Cima KM, Löffler‑Ragg J, Hilbe W, Zwierzina H, Zwierzina H, et al: Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells. Oncol Lett 14: 5563-5568, 2017
APA
Gamerith, G., Amann, A., Schenk, B., Auer, T., Lentzen, H., Mügge, D.O. ... Zwierzina, H. (2017). Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells. Oncology Letters, 14, 5563-5568. https://doi.org/10.3892/ol.2017.6861
MLA
Gamerith, G., Amann, A., Schenk, B., Auer, T., Lentzen, H., Mügge, D. O., Cima, K. M., Löffler‑Ragg, J., Hilbe, W., Zwierzina, H."Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells". Oncology Letters 14.5 (2017): 5563-5568.
Chicago
Gamerith, G., Amann, A., Schenk, B., Auer, T., Lentzen, H., Mügge, D. O., Cima, K. M., Löffler‑Ragg, J., Hilbe, W., Zwierzina, H."Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells". Oncology Letters 14, no. 5 (2017): 5563-5568. https://doi.org/10.3892/ol.2017.6861