Effect of double-stranded DNA on maturation of dendritic cells in vitro

Alyamkina, E. A.; Леплина, О. Ю.; Сахно, Л. В.; Черных, Е. Р.; Останин, А. А.; Efremov, Yaroslav R.; Shilov, A.G.; Proskurina, Anastasia S.; Orishchenko, Кonstantin E.; Долгова, Е. В.; Рогачев, В. А.; Николин, В. П.; Попова, Н. А.; Zagrebelniy, Stanislav N.; Богачев, С. С.; Shurdov, Mikhail A.

doi:10.1016/j.cellimm.2010.08.011

Cited by 14 publications

(13 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Proceeding on reported observations [14,39,47], we assumed that this inhibition may be due to the inducer effect of dsDNA on DC maturation in vivo that causes effective presentation of antigens of tumor lysate and activates antitumor mechanisms of the adaptive immunity.…”

Section: Resultsmentioning

confidence: 99%

A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation

Alyamkina

Николин

Попова

et al. 2010

Genet Vaccines Ther

View full text Add to dashboard Cite

BackgroundImmunization of mice with tumor homogenate after combined treatment with cyclophosphamide (CP) and double-stranded DNA (dsDNA) preparation is effective at inhibition of growth of tumor challenged after the treatment. It was assumed that this inhibition might be due to activation of the antigen-presenting cells. The purpose was to develop improved antitumor strategy using mice. We studied the combined action of cytostatics doxorubicin (Dox) plus CP with subsequent dsDNA preparation on tumor growth.MethodsThree-month old CBA/Lac mice were used in the experiments. Mice were injected with CP and human dsDNA preparation. The percentage of mature dendritic cells (DCs) was estimated by staining of mononuclear cells isolated from spleen and bone marrow 3, 6, and 9 days later with monoclonal antibodies CD34, CD80, and CD86. In the next set of experiments, mice were given intramuscularly injections of 1-3 × 105 tumor cells. Four days later, they were injected intravenously with 6-6.7 mg/kg Dox and intraperitoneally with 100-200 mg/kg CP; 200 mkg human DNA was injected intraperitoneally after CP administration. Differences in tumor size between groups were analyzed for statistical significance by Student's t-test. The MTT-test was done to determine the cytotoxic index of mouse leucocytes from treated groups.ResultsThe conducted experiments showed that combined treatment with CP and dsDNA preparation produce an increase in the total amount of mature DCs in vivo. Treatment of tumor bearers with preparation of fragmented dsDNA on the background of pretreatment with Dox plus CP demonstrated a strong suppression of tumor growth in two models. RLS, a weakly immunogenic, resistant to alkalyting cytostatics tumor, grew 3.4-fold slower when compared with the control (p < 0.001). In experiment with Krebs-2 tumor, only 2 of the 10 mice in the Dox+CP+DNA group had a palpable tumor on day 16. The cytotoxic index of leucocytes was 86.5% in the Dox+CP+DNA group, but it was 0% in the Dox+CP group.ConclusionsThus, the set of experiments we performed showed that exogenous dsDNA, when administered on the background of pretreatment with Dox plus CP, has an antitumor effect possibly due to DC activation.

show abstract

Section: Resultsmentioning

confidence: 99%

A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation

Alyamkina

Николин

Попова

et al. 2010

Genet Vaccines Ther

View full text Add to dashboard Cite

show abstract

“…When dsDNA preparations from various sources were compared, human dsDNA consistently displayed superior leukostimulatory and anti-tumor activity [ 7 - 9 , 12 - 17 ].…”

Section: Resultsmentioning

confidence: 99%

“… Activation of antigen-presenting dendritic cells and expansion of a population of cytotoxic perforin + CD8+ T cells contribute to the anticancer activity of Panagen. These features are based on the interaction of Panagen dsDNA fragments with dendritic cells, which in turn activates their antigen-presenting properties [ 7 - 9 , 12 , 13 ]. So-called “delayed death” phenomenon results from the selective targeting of CD34+ hematopoietic stem cells as they recover from the genotoxic stress caused by a cross-linking agent cyclophosphamide.…”

Section: Resultsmentioning

confidence: 99%

“…In terms of inducing adaptive (anticancer) immune response, the major steps of dsDNA therapeutic activity in combination with cross-linking and anthracycline cytostatics are as follows: Human dsDNA potently activates dendritic cells [ 7 - 9 , 12 , 13 ]. Upon oral administration, dsDNA reaches the immune cells of intestinal mucosa and stimulates their professional properties [ 41 - 48 ].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Results of multicenter double-blind placebo-controlled phase II clinical trial of Panagen preparation to evaluate its leukostimulatory activity and formation of the adaptive immune response in patients with stage II-IV breast cancer

et al. 2015

View full text Add to dashboard Cite

BackgroundWe 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.MethodsPatients 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.ResultsPanagen 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.ConclusionsThe 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.Trial registrationClinicalTrials.gov NCT02115984 from 04/07/2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1142-z) contains supplementary material, which is available to authorized users.

show abstract

“…Thus, recent studies revealed that intracellular dsDNA can lead to DC maturation. [29][30] In 1 of these studies, 30 dsDNA was shown to be a potent activator of human monocyte-derived DCs and primary DCs leading to potent immunostimulatory cells. Activation by dsDNA has been shown to depend on NF-κB activation, and partially, on the novel cytosolic dsDNA receptor interferon-inducible protein 16, but not on the previously recognized dsDNA sentinels AIM2, a finding that, according to the authors' conclusion, cannot exclude the existence of a yet-to-be-identified cytosolic DNA sensor(s).…”

Section: Oxidative Allograft Injurymentioning

confidence: 99%

Future Immunosuppression in Organ Transplantation: Treating the Innate Immune System of the Deceased Donor - Start Tomorrow

Land¹

2012

Exp Clin Transplant

View full text Add to dashboard Cite

Effect of double-stranded DNA on maturation of dendritic cells in vitro

Cited by 14 publications

References 53 publications

A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation

A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation

Results of multicenter double-blind placebo-controlled phase II clinical trial of Panagen preparation to evaluate its leukostimulatory activity and formation of the adaptive immune response in patients with stage II-IV breast cancer

Future Immunosuppression in Organ Transplantation: Treating the Innate Immune System of the Deceased Donor - Start Tomorrow

Contact Info

Product

Resources

About