Modern strategies and capabilities for activation of the immune response against tumor cells.

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.

Induction of an antitumor response using dendritic cells transfected with DNA constructs encoding the HLA-A*02:01-restricted epitopes of tumor-associated antigens in culture of mononuclear cells of breast cancer patients.

Advances in oncoimmunology related to the definition of the basic mechanisms of the formation of antitumor immune response, as well as the opening of tumor-associated antigens recognized by immune cells, allowed to start developing ways to influence the effector cells of the immune system to generate effective antitumor cytotoxic response. We investigated the possibility to stimulate an antitumor response in a culture of mononuclear cells of breast cancer patients by dendritic cells transfected with HLA-A*02:01-restricted DNA constructs. We isolated dendritic cells from peripheral blood monocytes and delivered our constructs to these cells by magnetic transfection. Additionally, a series of experiments with loading of dendritic cells with autologous tumor cell lysate antigens was conducted. We have shown that dendritic cells transfected with the HLA-A*02:01-restricted DNA constructs are effective in inducing an antitumor response in a culture of mononuclear cells of breast cancer patients. Dendritic cells transfected with DNA constructor dendritic cells loaded with lysate antigens revealed a comparable stimulated cytotoxic response of mononuclear cells to these two ways of antigen delivery. We conclude that using DNA constructs in conjunction with patient stratification by HLA type allows the application of transfected DCs as an effective method to stimulate antitumor immunity in vitro.