[Features of functional activity of dendritic cells in tumor growth].

During recent years much data, accumulated on biology, function and role of dendritic cells (DC) in cancer development, in a new way allow assessing their role in disease process. Identification of features of DC functional state as well as their interaction and influence on the immune cells in tumor growth can be used as a basis for a new approach to cancer therapy enhancing standard therapy efficacy. The review analyzes different mechanisms of escaping of tumor cell from immune surveillance involving DC as one of the main participants of antitumor immune response. Also the prospects of using DC for vaccination are discussed. DC can be promising target for therapeutic strategies and also can be used for formation of antitumor response and cell therapy.

Dendritic Cells Transfected with a DNA Construct Encoding Tumour-associated Antigen Epitopes Induce a Cytotoxic Immune Response Against Autologous Tumour Cells in a Culture of Mononuclear Cells from Colorectal Cancer Patients.

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 DNA-transfected 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 perforin-positive 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.

Effect of mature dendritic cells primed with autologous tumor antigens from patients with epithelial ovarian cancer on stimulation of the cytotoxic immune response in culture of mononuclear cells.

For modulation of antitumor cytotoxic activity of mononuclear cells in vitro, autologous dendritic cells loaded with tumor lysate antigens were cultured with peripheral blood mononuclear cells from patients with epithelial ovarian cancer in the presence or absence of IL-12 and IL-18. The efficiency of modulation was evaluated by cytotoxic activity of mononuclear cells against autologous tumor cells, by the production of IFN-γ, IL-4, and by the count of perforin-containing lymphocytes. It was demonstrated that dendritic cells stimulated cytotoxic immune response in mononuclear cell culture. Maximum induction of cytotoxic activity of mononuclear cells was attained in case of dendritic cells combination with IL-12 and IL-18 (increased death of autologous tumor cells, accumulation of perforin-positive lymphocytes, enhanced production of IFN-γ).