No abstract

Significant effort has been devoted to developing effective cancer vaccines based on dendritic cells (DCs) loaded with various tumour antigens, including DNA constructs that carry sequences of tumour-associated antigens (TAAs). Such vaccines efficiently and selectively activate the T cell immune response. In this study, we describe a method to induce an antitumour immune response in mononuclear cell (MNC) cultures from colorectal cancer patients using DNAtransfected DCs encoding TAA epitopes of carcinoembryonic antigen, epithelial cell adhesion molecule and mucin 4. DCs were obtained from peripheral blood monocytes of colorectal cancer patients. Magnetic-assisted transfection was used to deliver the genetic constructs to DCs. To assess the potency of the immune response, the antitumour cytotoxic response was assessed by lymphocyte intracellular perforin and the MNC cytotoxic activity against autologous tumour cells. We showed that polyepitope DNA-transfected DCs enhanced MNC antitumour activity, increasing tumour cell death and the percentage of perforinpositive lymphocytes. In addition, DNA-transfected DCs elicited a cytotoxic response that was as efficient as that of tumour lysate-loaded DCs. Taken together, the data suggest that it is feasible to induce an antitumour immune response in colorectal MNCs using transfected DCs. Thus, the DNA construct reported in this study may potentially be used in therapeutic and prophylactic DC-based vaccines.

Abstract.Cancer is associated with a reduction in immature and mature circulating dendritic cells (DCs), and with an impaired migratory capacity, compared with healthy donors. Therefore, modern approaches to the in vitro generation of DCs loaded with tumor antigens and their use for inducing antitumor immune responses in vivo are being investigated. The purpose of the present study was to investigate the phenotypic and functional characteristics of peripheral blood DC subsets in patients with non-small cell lung cancer (NSCLC), and the development of an antitumor cytotoxic response by mononuclear cells (MNCs) from patients using in vitro generated antigen-primed DCs. Heparinized peripheral venous blood samples were obtained from 10 healthy donors and 20 patients with a histologically verified diagnosis of NSCLC. The ability of antigen-activated DCs to stimulate the activity of MNCs against autologous tumor cells was evaluated using a cytotoxic test. Peripheral blood DC subsets from patients with NSCLC were identified to be decreased and to exhibit an impaired ability to mature, compared with healthy donors. Furthermore, DCs generated from MNCs from patients with NSCLC were able to stimulate a specific cytotoxic response when loaded with autologous tumor lysates or RNA and matured, in vitro. A perforin and granzyme B-dependent mode of cytotoxicity was primarily induced. The ability of DCs loaded with tumor antigens to increase the cytotoxic activity of MNCs against NSCLC cells in vitro indicates the effective induction and co-stimulation of T lymphocytes by the generated DCs.

Dendritic cells are professional antigen-presenting cells and the most potent stimulators of various immune responses, such as antitumor responses. Modern studies have not shown an effective antitumor immune response development in patients with malignant tumors. The major cause is the decrease in functional activity of dendritic cells in cancer patients through irregularities in the maturation process to a functionally active form and in the antigen presentation process to naive T lymphocytes. This review describes the main stages of cellular antitumor immune response induction in vitro, aimed at resolving the problems that are blocking the full functioning of dendritic cells, and additional stimulation of antitumor immune response.

The aim of the study is justified by the need to create modern personnel competencies for the digital economy and create a new model of modern universities. Strengthening the role of the university, as one of the main producers of knowledge and competencies for the information society, dictates the need for it to implement both the functions of education and research, as well as the functions of transfer, commercialization of technology, and a provider of knowledge about the future. The purpose of the study is to analyse the role of electronic forms of learning and the functioning of the electronic educational system in the prospects for the establishment of University 4.0, and also to identify what the electronic information and educational environment in a new generation of higher education should be like. The methodological basis of the work is the analytical and systemic approaches to the study of the object of study using the methods of logical and causal analysis, expert assessments and systematization of data. The article discusses the specific experience of the development and implementation of e-learning in Peter the Great St. Petersburg Polytechnic University (SPbPU). The authors analyse the effectiveness of the interaction of participants in the educational process within the framework of the electronic information educational environment, changes in the personnel policy, issues of staff development, the creation of a developed ICT infrastructure and the prospects for promoting large-scale modernization of the university. Based on the analysis of the experience of development and implementation at electronic information educational environment in SPbPU, the article highlights the advantages and disadvantages of using digital technologies in the educational activities of the university considering the challenges of its modernization. The authors concluded that the electronic educational environment is effective both in the educational process of the university and in increasing the competitiveness of the university in the modern digital market, in fulfilling the functions of transfer, commercialization of technologies and a provider of knowledge about the future.