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Updated: Aug 19, 2025
Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
Published on: May 31, 2018
Dendritic Cell-Derived Artificial Microvesicles Inhibit RLS40 Lymphosarcoma Growth in Mice via Stimulation of
Oleg V Markov1, Aleksandra V Sen'kova1, Islam S Mohamed1
1Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva Ave. 8, 630090 Novosibirsk, Russia.
Abstract:
Cell-free antitumor vaccines represent a promising approach to immunotherapy of cancer. Here, we compare the antitumor potential of cell-free vaccines based on microvesicles derived from dendritic cells (DCs) with DC- and cationic-liposome-based vaccines using a murine model of drug-resistant lymphosarcoma RLS40 in vivo. The vaccines were the following: microvesicle vaccines—cytochalasin B-induced membrane vesicles (CIMVs) obtained from DCs loaded with total tumor RNA using cholesterol/spermine-containing cationic liposomes L or mannosylated liposomes ML; DC vaccines—murine DCs loaded with total tumor-derived RNA using the same liposomes; and liposomal vaccines—lipoplexes of total tumor-derived RNA with liposomes L or ML. Being non-hepatotoxic, CIMV- and DC-based vaccines administered subcutaneously exhibited comparable potential to stimulate highly efficient antitumor CTLs in vivo, whereas liposomal vaccines were 25% weaker CTL inducers. Nevertheless, the antitumor efficiencies of the different types of the vaccines were similar: sizes of tumor nodes and the number of liver metastases were significantly decreased, regardless of the vaccine type. Notably, the booster vaccination did not improve the overall antitumor efficacy of the vaccines under the study. CIMV- and DC- based vaccines more efficiently than liposome-based ones decreased mitotic activity of tumor cells and induced their apoptosis, stimulated accumulation of neutrophil inflammatory infiltration in tumor tissue, and had a more pronounced immunomodulatory activity toward the spleen and thymus. Administration of CIMV-, DC-, and liposome-based vaccines resulted in activation of Th1/Th17 cells as well as the induction of positive immune checkpoint 4-1BBL and downregulation of suppressive immune checkpoints in a raw PD-1 >>> TIGIT > CTLA4 > TIM3. We demonstrated that cell-free CIMV-based vaccines exhibited superior antitumor and antimetastatic activity in a tumor model in vivo. The obtained results can be considered as the basis for developing novel strategies for oncoimmunotherapy.
Insights
Cell-free vaccines using microvesicles from dendritic cells (DCs) show superior antitumor and antimetastatic effects compared to liposome-based vaccines. These microvesicle vaccines effectively stimulate immune responses against drug-resistant lymphosarcoma in vivo.
Area of Science:
- Oncology
- Immunotherapy
- Nanotechnology
Background:
- Cell-free vaccines are a promising cancer immunotherapy strategy.
- Dendritic cell (DC)-derived microvesicles offer a novel cell-free vaccine platform.
- Comparing different cell-free vaccine formulations is crucial for optimizing cancer treatment.
Purpose of the Study:
- To compare the antitumor efficacy of microvesicle-based vaccines with DC- and liposome-based vaccines.
- To evaluate vaccine-induced immune responses in a murine model of drug-resistant lymphosarcoma.
- To investigate the immunomodulatory effects and immune checkpoint modulation of different vaccine types.
Main Methods:
- Utilized cytochalasin B-induced membrane vesicles (CIMVs) from RNA-loaded DCs and liposomal formulations.
- Employed a murine model of drug-resistant lymphosarcoma RLS40 for in vivo studies.
- Assessed antitumor activity, metastasis reduction, immune cell activation (CTLs, Th1/Th17), and immune checkpoint expression.
Main Results:
- CIMV- and DC-based vaccines demonstrated comparable, potent induction of antitumor cytotoxic T lymphocytes (CTLs), outperforming liposomal vaccines.
- All vaccine types significantly reduced tumor size and liver metastases, with CIMV- and DC-based vaccines showing enhanced effects on tumor cell apoptosis and immune infiltration.
- Vaccine administration modulated immune checkpoints, including upregulation of 4-1BBL and downregulation of PD-1, TIGIT, CTLA4, and TIM3.
Conclusions:
- Cell-free CIMV-based vaccines exhibit superior antitumor and antimetastatic activity compared to liposome-based vaccines in a preclinical model.
- These findings support the development of novel oncoimmunotherapy strategies utilizing DC-derived microvesicles.
- Booster vaccination did not significantly enhance the overall antitumor efficacy in this study.
