Kiandokht Borhani; Taravat Bamdad; Tayebeh Hashempour
Volume 14, Issue 2 , June 2017, , Pages 151-158
Abstract
Background: 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 ...
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Background: 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 in vitro and in vivo. Objective: To evaluate the in vitro impact of lenalidomide, of different doses, on NK cytotoxicity activity and an in vivo investigation to find the adjuvant behavior of lenalidomide. Methods: 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 in vitro 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. Results: 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 in vivo, augmenting it from 16.67% ± 2.07% for the control group to 38.17% ± 2.87% for the lenalidomide-treated. Conclusion: 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.
Mohsen Mohammadi; Zahra Kianmehr; Sussan Kaboudanian Ardestani; Behnaz Gharegozlou
Volume 11, Issue 3 , September 2014, , Pages 189-199
Abstract
Background: Adjuvants are used to increase the immunogenicity of new generation vaccines, especially those based on recombinant proteins. Despite immunostimulatory properties, the use of bacterial lipopolysaccharide (LPS) as an adjuvant has been hampered due to its toxicity and pyrogenicity. Brucella ...
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Background: Adjuvants are used to increase the immunogenicity of new generation vaccines, especially those based on recombinant proteins. Despite immunostimulatory properties, the use of bacterial lipopolysaccharide (LPS) as an adjuvant has been hampered due to its toxicity and pyrogenicity. Brucella abortus LPS is less toxic and has no pyrogenic properties compared to LPS from other gram negative bacteria. Objectives: To evaluate the adjuvant effect of B. abortus (vaccine strain, S19) LPS for tetanus toxoid antigen (TT) and to investigate the protective effect of different tetanus vaccine preparations. Methods: LPS was extracted and purified from B. abortus S19 and KDO, glycan, phosphate content, and protein contamination were measured. Adipic acid dihydrazide (ADH) was used as a linker for the conjugation of TT to LPS. Different amounts of B. abortus LPS, TT, TT conjugated with LPS, and TT mixed with LPS or complete Freund’s adjuvant (CFA) were injected into mice and antibody production against TT was measured. The protective effect of induced antibodies was determined by LD50. Results: Immunization of mice with TT+LPS produced the highest anti-TT antibody titer in comparison to the group immunized with TT without any adjuvant or the groups immunized with TT-LPS or TT+CFA. Tetanus toxid-S19 LPS also produced a 100% protective effect against TT in immunized mice. Conclusion: These data indicate that B. abortus LPS enhances the immune responses to TT and suggest the possible use of B. abortus LPS as an adjuvant in vaccine preparations.
Rohollah Dorostkar; Taravat Bamdad; Masoud Parsania; Hassan Pouriayevali
Volume 9, Issue 4 , December 2012, , Pages 215-225
Abstract
Background: Improving vaccine potency in the induction of a strong cell-mediated cytotoxicity can enhance the efficacy of vaccines. Necrotic cells and the supernatant of necrotic tumor cells are attractive adjuvants, on account of their ability to recruit antigen-presenting cells to the site of antigen ...
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Background: Improving vaccine potency in the induction of a strong cell-mediated cytotoxicity can enhance the efficacy of vaccines. Necrotic cells and the supernatant of necrotic tumor cells are attractive adjuvants, on account of their ability to recruit antigen-presenting cells to the site of antigen synthesis as well as its ability to stimulate the maturation of dendritic cells. Objective: To evaluate the utility of supernatant of necrotic tumor cells as a DNA vaccine adjuvant in a murine model. Method: The supernatant of EL4 necrotic cells was co-administered with a DNA vaccine expressing the glycoprotein B of Herpes simplex virus-1 as an antigen model under the control of Cytomegalovirus promoter. C57BL/6 mice were vaccinated three times at two weeks intervals with glycoprotein B DNA vaccine and supernatant of necrotic EL4 cells. Five days after the last immunization, cell cytotoxicity, IFN-γ and IL-4 were evaluated. Results: The obtained data showed that the production of IFN-γ from the splenocytes after antigenic stimulation in the presence of the supernatant of necrotic EL4 cells was significantly higher than the other groups (p<0.002). The flow cytometry results showed a significant increase in the apoptosis/necrosis of EL4 cells in the mice immunized with DNA vaccine and supernatant of necrotic EL4 cells comparing to the other groups (p<0.001). Conclusion: The supernatant of necrotic cells contains adjuvant properties that can be considered as a candidate for tumor vaccination.
