Dendritic cell (DC)-based immunotherapy represents a promising approach for cancer treatment. However, the DC homing rate to the lymphoid tissues is poor, thus hindering the activation of antigen-specific T cells and reducing their antitumor efficacy. Here, we developed an approach based on magnetic nanoparticles (NP) to manipulate DC migration and thus elicit a more robust and efficacious antitumor response in tumor-bearing mice.
Mouse spleen DCs were loaded with nanocomplexes (NC) consisting of iron oxide NP (8x10−12 g/cell) and lyophilized tumor tissue. To investigate the presence of NP in DCs, the method of Fe2+ and Fe3+ detection by Prussian Blue Staining was used. DCs were injected intradermally into tumor-bearing mice three times in an amount of 2x105 per mouse at an interval of 3 days starting from day 7 after Lewis lung carcinoma inoculation. One group of mice that received DCs loaded with NC was exposed to a magnetic field for 1 h. The number and volume of metastases and tumor weight were assessed 28 days after tumor inoculation. At the same time, the levels of INF-γ, IL-10, TGF-ß, IL-4, FoxP3 mRNA expression in the spleen and inguinal lymph nodes were determined.
The iron oxide NP showed no toxic effects on the DCs and had no effect on their viability. We found that almost all DCs are able to incorporate magnetic NP after 24h of incubation. Fewest metastases were found in the mice that received DCs loaded with NC and were exposed to a magnetic field: the number of metastases in mice from this group was 1.7 times less than in control mice. It should be noted that the volume of metastatic nodes in the lungs and the mass of the primary tumor were practically the same as in the control mice. The most pronounced decrease in FoxP3 mRNA levels in the lymph nodes, indicating a decrease in the activity of regulatory T cells, was also noted in the mice receiving DCs loaded with nanocomplexes and exposed to a magnetic field. In the mice of this group, a significant decrease in the level of IL-4 in the spleen was detected.
Our results suggest that an approach based on magnetic NC could be a promising strategy for improving the antitumor efficacy of DC-based immunotherapy.
Clinical trial identification
Legal entity responsible for the study
National Cancer Institute of Ministry of Public Health of Ukraine
All authors have declared no conflicts of interest.