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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.
Pharmaceutics
|November 26, 2022
Summary
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.
