Low Dose of Lenalidomide Enhances NK Cell Activity: Possible Implication as an Adjuvant

• Main Authors: Kiandokht Borhani, Taravat Bamdad, Tayebeh Hashempour
• Format: Article
• Language: English
• Published: Shiraz University of Medical Sciences 2017-06-01
• Series: Iranian Journal of Immunology
• Subjects: Lenalidomide; NK cell; Adjuvant; LDH test
• Online Access: http://iji.sums.ac.ir/article_39305_6d3e722f67151005e60e2095c02f8d60.pdf
• ISSN: 1735-1383; 1735-367X

<strong>Background:</strong> Lenalidomide, a synthetic immunomodulatory drug, has a wide range of features including anti-angiogenic and anti-proliferative properties. To date, researchers have shown that lenalidomide is capable of ameliorating the immune system factors and antitumor responses. Most researchers have reported that lenalidomide enhances the immune response in certain cancer patients through several pathways including the stimulation of Natural Killer cells; notwithstanding, it is still crucial to investigate the effect of lenalidomide on the activity of NK cell cytotoxicity both <em>in vitro</em> and <em>in vivo</em>.<strong> Objective:</strong> To evaluate the <em>in vitro</em> impact of lenalidomide, of different doses, on NK cytotoxicity activity and an <em>in vivo</em> investigation to find the adjuvant behavior of lenalidomide. <strong>Methods:</strong> NK cytotoxocity was measured with the lactate dehydrogenase (LDH) release assay via K562 cells. Lenalidomide was prepared at 1 mM, 2 mM, 4 mM and 8 mM for <em>in vitro</em> study. In addition, the adjuvant properties of lenalidomide were assessed in ten mice groups using NS3 HCV DNA vaccine model of antigen pcDNA3.1(+)/NS3.<strong> Results:</strong> The results showed that, comparisons to other doses, 4 mMol of lenalidomide was able to noticeably increase NK cytotoxicity activity. Furthermore, the animal model indicated that lenalidomide stimulated NK cytotoxicity <em>in vivo</em>, augmenting it from 16.67% ± 2.07% for the control group to 38.17% ± 2.87% for the lenalidomide-treated.<strong> Conclusion:</strong> Treatment by lenalidomide and pcDNA3.1(+)/NS3 improves NK cytotoxicity up to 66.80% suggesting that lenalidomide can be used in parallel with such therapeutic vaccines as cancer vaccine or virus vaccines.