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Information × Registration Number 0219U001574, 0116U002409 , R & D reports Title To develop and justify the feasibility of modern nano- and cellular technologies to enhance the anticancer and immunomodulatory properties of vaccines based on dendritic cells popup.stage_title Head Khranovska Natalia, Registration Date 07-02-2019 Organization Ukrainian Research Institute of Oncology and Radiology popup.description2 Objects of the study - dendritic cells, magnetic nanocomplex, biodegradable nanoparticles, antitumor vaccines, experimental tumors (Lewis lung carcinoma, sarcoma 37). The aim of the study - to increase the antitumor and immunomodulatory properties of vaccines based on dendritic cells created with engagement of up-to-date nano- and cellular technologies, to investigate their biological properties, and to rationalize their using in anti-tumor immunotherapy. Methods - methods of experimental oncology, cell culture, flow cytometry, immunological, molecular-genetic and statistical methods. Dendritic cells (DCs) from cancer patients, according to their phenotypic properties refer to cells of middle degree of maturity and express an elevated mRNA level of cytokines TGF-?, IL-10 and the IDO enzyme, and they are characterized by reduced ability to produce IL-12. The combination of IFN-? and LPS promotes Th1-polarization of generated DCs without inducing their tolerogenic properties. St. aureus Wood 46 extract of cytoplasmic membranes (ECM) have been found to significantly increase the expression of CD86 and HLA-DR molecules on the generated DCs and decrease their phagocytic activity. It has been shown that the combination of IFN-? (10,000 IU/ml) and ECM increases the expression of Th1-polarizing cytokines and increases the CCR7 chemokine expression. The magnetic nanocomplex (MNC)technology is developed, which includes the lyophilized tumor cells and nanoparticles (NP) of iron oxide Fe2O3 mechanical treatment with MMVE-0,005micro mill.The most optimal concentration of iron oxide NP for generated DC loading, which is 8*10-12 g/ml, is determined. Moreover, the Lille staining technique for staining of DC with NP was developed. Newanti-tumour vaccines based on mouse DC and MNC have been created using sarcoma 37 or Lewis lung carcinoma cells. In mice with Lewis carcinoma, the combined effect of DC vaccine and magnetic field contributed to a significant decrease of IL-4 mRNA, increase of IFN-? mRNA levels and decrease of TGF-? and FoxP3 transcription factor mRNA expression in the spleen and lymph nodes. Antitumor effect of DCs loaded with MNC without and under magnetic field control was associated with a significant decrease in expression level of FoxP3 and IL-10 mRNA in lymph node cells. Some increase in the lymph nodes size was also revealed in mice with Sa 37.The technology of NP obtaining from copolymers of lactic and glycolic acids (PLGA) and tumor cells lysate was developed As a result of human DCs loading by PLGA-NP, the levels of CD86, HLA-DR, HLA-ABC and CD83 maturation molecules expression increased by 15-20%, indicating their stimulating effect on the DCs maturation. Product Description popup.authors Іномістова М.В. Горбач О. Скачкова О.В. Храновська Н.М. popup.nrat_date 2020-04-02 Close