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

Gamerith,Gabriele; Amann,Arno; Schenk,Bettina; Auer,Thomas; Lentzen,Hans; Mügge,Dirk  O.; Cima,Katharina  M.; Löffler‑Ragg,Judith; Hilbe,Wolfgang; Zwierzina,Heinz

doi:10.3892/ol.2017.6861

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
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Affiliations: Clinic of Internal Medicine V, Innsbruck Medical University, A‑6020 Innsbruck, Austria, Department of General and Surgical Critical Care Medicine, Innsbruck University, A‑6020 Innsbruck, Austria, Department of Radiology, Innsbruck Medical University, A‑6020 Innsbruck, Austria, MELEMA Pharma GmbH, G‑20148 Hamburg, Germany, Institute of Psychology, Innsbruck University, A‑6020 Innsbruck, Austria, Clinic of Internal Medicine VI, Innsbruck Medical University, A‑6020 Innsbruck, Austria, Clinic of Internal Medicine I, Wilhelminenspital Wien, A‑1160 Vienna, Austria
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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