Maturation and Antigen Loading Protocols Influence Activity of Anticancer Dendritic Cells

• Published in: Molecular biology (New York) Vol. 52; no. 2; pp. 222 - 231
• Main Authors: Nazarkina, Zh. K., Zajakina, A., Laktionov, P. P.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.03.2018; Springer Nature B.V
• Subjects: Antigen (tumor-associated); Biochemistry; Biomedical and Life Sciences; Cancer; Cell activation; Dendritic cells; Deoxyribonucleic acid; DNA; Human Genetics; Immune response; Immune response (cell-mediated); Interleukin 10; Interleukin 12; Interleukin 6; Life Sciences; Lymphocytes T; Molecular Cell Biology; Nucleic acids; Polyinosinic:polycytidylic acid; Prostaglandin E2; Ribonucleic acid; RNA; Surface markers; T cell receptors; Transfection; Tumor necrosis factor-α; Vaccines; α-Interferon; γ-Interferon; antigen delivery; anticancer immunotherapy; dendritic cells; cytotoxic T lymphocytes
• ISSN: 0026-8933; 1608-3245
• DOI: 10.1134/S0026893317050132

The practical use of dendritic cell-based vaccines in anticancer therapy is limited by a lack of standards for dendritic cell (DC) generation, as well as standard procedures for controlling their activation and the technique of DC loading with nucleic acids encoding tumor antigens. Analyzing the currently available data, the most promising cocktails for DC maturation were selected and a comparative study of the cocktails and time of maturation on the capacity of DC to activate T-cell immune response has been performed. A study of the expression of surface markers and the production of IL-12, IL-6, and IL-10 cytokines, as well as the efficacy of T-cell activation showed that the use of the standard 7-day maturation protocol is preferable to the 4-day maturation protocol. Cocktails composed of TNF-α, IL-1β, IFN-α, IFN-γ, and poly(I:C), as well as TNF-α, IL-1β, IFN-γ, R848, and PGE2 were shown to be the most efficient activators of DCs. A comparison of the efficacy of different methods of DNA transfection into DCs and RNA delivery using alphavirus vectors demonstrated the superiority of magnet-assisted transfection (MATra) to other protocols.