Abstract 5500
Background
One of the approaches for increasing DC vaccine efficacy is the direct delivery of generated DC to the regional lymph nodes and tumor site. The aim was to investigate the antitumor efficacy of DC loaded with tumor antigens and iron oxide nanoparticles (INP) under the influence of an external magnetic field.
Methods
In experimental study, 60 CBA mice were involved. Sarcoma 37 (S37) was used as experimental tumor model, and cells in lethal dose (9*105 cells per animal) were injected into the hip. DCs were obtained from syngeneic mice splenocytes and loaded by mechanically modified lyophilized Sa 37 cells (0.05 mg/ml) with Fe2O3 nanoparticles (8x10-12 g/cell, Sigma-Aldrich). DC vaccine was injected intradermally 3 times with three-day interval starting on the 7th day after tumor transplantation. After DC administration, animals were exposed under magnetic field for 1 hour. Tumor volume was evaluated with three days interval starting after 10 days of tumor transplantation. Tumor mass, leukocyte formula of the peripheral blood and absolute number of cells in the lymphoid organs of animals were assessed at the 25th day of the experiment. The expression levels of GAPDH, FOXP3, VEGF-a, IL-10, TGF-b, IFNγ and IL-4 genes were analyzed in tumor, spleen and regional lymph nodes using a quantitative PCR method.
Results
The application of generated DCs with INP promoted a reduction of primary tumor volume compared to the control group (p = 0,022) and DC monotherapy (p = 0.005). DCs with INP didn’t significantly effect on the hematological parameters in mice with S37. The combined effect of DCs with INP reduced mRNA expression levels of FoxP3 by 1.9 times (p = 0.04), VEGF-α by 2.9 times (p = 0.02), IL-10 by 2.9 times (p = 0.005) and TGF-β by 10 times (p = 0.002) in tumor cells compared to the control. The administration of DC vaccine with INP led to reduce tumor immunosuppression in the regional lymph nodes, namely FoxP3 mRNA level decreased in 2,4 times and Il-10 mRNA level – in 1.9 times compared to the control group, p = 0.012.
Conclusions
Application of DC vaccine with INP under magnetic field resulted in a pronounced antitumor effect in tumor-bearing mice.
Clinical trial identification
Legal entity responsible for the study
National cancer institute of the MPH Ukraine.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.