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Novosibirsk, Russia

Orishchenko K.E.,RAS Institute of Cytology and Genetics | Ryzhikova S.L.,CJSC Vector best | Druzhinina Y.G.,CJSC Vector best | Ryabicheva T.G.,CJSC Vector best | And 16 more authors.
Cancer Therapy | Year: 2013

Nucleic acids of various origin and form are capable of activating the innate immune cells and inducing the development of the adaptive immune response. Here we demonstrated that fragments of double-stranded DNA (dsDNA) preparation reached the nuclear space of ex vivo generated human dendritic cells. We showed that dendritic cells generated according to two protocols using IL-4 or IFN-α, upon induction by dsDNA preparation, produced a broad array of cytokines (IFN-γ, MIP-1β, TNF-α, IL-6, G-CSF, and MCP-1). Culturing of human whole blood cells in the presence of dsDNA preparation gave rise to a spectrum of cytokines whose inductive strength considerably surpassed that of pharmacopoeian immunomodulatory preparations (Ridostin, Dezoxyl) and was comparable to that of poly(I):poly(C) preparation or a mixture of mitogens (PHA-P, PHA-M, ConA, and LPS mixture). In a group of relatively healthy donors (n=14), we showed that human dsDNA preparation induced the production of TNF-α, IFN-γ, IL-1RA, IL-1β, IL-6, IL-8, IL-10, G-CSF, and GM-CSF to a great extent and that of IFN-α, VEGF, MCP-1, and IL-18 to a lesser one or not in all the donors by peripheral blood mononuclear cells; human dsDNA preparation was without appreciable effect on the production of IL-2 and IL-17. It was slightly weaker than the standard inducer (the mitogen mixture) with respect to the inductive effect.

Proskurina A.S.,RAS Institute of Cytology and Genetics | Gvozdeva T.S.,Novosibirsk State Medical University | Alyamkina E.A.,RAS Institute of Cytology and Genetics | Dolgova E.V.,RAS Institute of Cytology and Genetics | And 16 more authors.
BMC Cancer | Year: 2015

Background: We performed a multicenter, double-blind, placebo-controlled, phase II clinical trial of human dsDNA-based preparation Panagen in a tablet form. In total, 80 female patients with stage II-IV breast cancer were recruited. Methods: Patients received three consecutive FAC (5-fluorouracil, doxorubicin and cyclophosphamide) or AC (doxorubicin and cyclophosphamide) adjuvant chemotherapies (3 weeks per course) and 6 tablets of 5 mg Panagen or placebo daily (one tablet every 2-3 hours, 30 mg/day) for 18 days during each chemotherapy course. Statistical analysis was performed using Statistica 6.0 software, and non-parametric analyses, namely Wilcoxon-Mann-Whitney and paired Wilcoxon tests. To describe the results, the following parameters were used: number of observations (n), median, interquartile range, and minimum-maximum range. Results: Panagen displayed pronounced leukostimulatory and leukoprotective effects when combined with chemotherapy. In an ancillary protocol, anticancer effects of a tablet form of Panagen were analyzed. We show that Panagen helps maintain the pre-therapeutic activity level of innate antitumor immunity and induces formation of a peripheral pool of cytotoxic CD8+ perforin + T-cells. Our 3-year follow-up analysis demonstrates that 24% of patients who received Panagen relapsed or died after the therapy, as compared to 45% in the placebo cohort. Conclusions: The data collected in this trial set Panagen as a multi-faceted "all-in-one" medicine that is capable of simultaneously sustaining hematopoiesis, sparing the innate immune cells from adverse effects of three consecutive rounds of chemotherapy and boosting individual adaptive immunity. Its unique feature is that it is delivered via gastrointestinal tract and acts through the lymphoid system of intestinal mucosa. Taken together, maintenance of the initial levels of innate immunity, development of adaptive cytotoxic immune response and significantly reduced incidence of relapses 3 years after the therapy argue for the anticancer activity of Panagen. © 2015 Proskurina et al.; licensee BioMed Central.

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