title: 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.
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 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.
authors.affiliation: Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology", Novosibirsk, Russian Federation.
authors.forename: E V
authors.initials: EV
authors.lastname: Kulikova
authors.affiliation: Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology", Novosibirsk, Russian Federation.
authors.forename: V V
authors.initials: VV
authors.lastname: Kurilin
authors.affiliation: Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology", Novosibirsk, Russian Federation.
authors.forename: J A
authors.initials: JA
authors.lastname: Shevchenko
authors.affiliation: Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology", Novosibirsk, Russian Federation.
authors.forename: I A
authors.initials: IA
authors.lastname: Obleukhova
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation.
authors.forename: E A
authors.initials: EA
authors.lastname: Khrapov
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation.
authors.forename: U A
authors.initials: UA
authors.lastname: Boyarskikh
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation.
authors.forename: M L
authors.initials: ML
authors.lastname: Filipenko
authors.affiliation: City Clinical Hospital No. 1, Novosibirsk, Russian Federation.
authors.forename: R V
authors.initials: RV
authors.lastname: Shorokhov
authors.affiliation: City Clinical Hospital No. 11, Novosibirsk, Russian Federation.
authors.forename: V K
authors.initials: VK
authors.lastname: Yakushenko
authors.affiliation: City Clinical Hospital No. 1, Novosibirsk, Russian Federation.
authors.forename: A V
authors.initials: AV
authors.lastname: Sokolov
authors.affiliation: Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology", Novosibirsk, Russian Federation.
authors.forename: S V
authors.initials: SV
authors.lastname: Sennikov
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D019496:Cancer Vaccines / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D000071858:Epithelial Cell Adhesion Molecule; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055264:Mucin-4 / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D000939:Epitopes; D055264:Mucin-4