title: 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.
abstract: 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.
authors.affiliation: Department of Molecular Immunology, Federal State Budgetary Institution "Research Institute of Fundamental and Clinical Immunology", Yadrintsevskaya St. 14, Novosibirsk, Novosibirsk, Russia, 630099. sennikovsv@gmail.com.
authors.forename: Sergey Vital'evich
authors.initials: SV
authors.lastname: Sennikov
authors.affiliation: Department of Molecular Immunology, Federal State Budgetary Institution "Research Institute of Fundamental and Clinical Immunology", Yadrintsevskaya St. 14, Novosibirsk, Novosibirsk, Russia, 630099.
authors.forename: Julia Alexandrovna
authors.initials: JA
authors.lastname: Shevchenko
authors.affiliation: Department of Molecular Immunology, Federal State Budgetary Institution "Research Institute of Fundamental and Clinical Immunology", Yadrintsevskaya St. 14, Novosibirsk, Novosibirsk, Russia, 630099.
authors.forename: Vasilii Vasil'evich
authors.initials: VV
authors.lastname: Kurilin
authors.affiliation: Department of Molecular Immunology, Federal State Budgetary Institution "Research Institute of Fundamental and Clinical Immunology", Yadrintsevskaya St. 14, Novosibirsk, Novosibirsk, Russia, 630099.
authors.forename: Julia Nikolaevna
authors.initials: JN
authors.lastname: Khantakova
authors.affiliation: Department of Molecular Immunology, Federal State Budgetary Institution "Research Institute of Fundamental and Clinical Immunology", Yadrintsevskaya St. 14, Novosibirsk, Novosibirsk, Russia, 630099.
authors.forename: Julia Anatol'evna
authors.initials: JA
authors.lastname: Lopatnikova
authors.affiliation: Vaccine Department, Avaxis Biotherapeutics LLC, Technopark St. 1 116, Koltsovo, Novosibirsk Region, Russia, 630559.
authors.forename: Elena Vasil'evna
authors.initials: EV
authors.lastname: Gavrilova
authors.affiliation: Vaccine Department, Avaxis Biotherapeutics LLC, Technopark St. 1 116, Koltsovo, Novosibirsk Region, Russia, 630559.
authors.forename: Rinat Amirovich
authors.initials: RA
authors.lastname: Maksyutov
authors.affiliation: Novosibirsk State University, Pirogova-90 St. 1, Novosibirsk, Russia.
authors.forename: Anastasiya Yur'evna
authors.initials: AY
authors.lastname: Bakulina
authors.affiliation: 3rd Oncological Department, City Clinical Hospital #1, Zalessky St. 6, Siberian Field, Novosibirsk, Russia, 630047.
authors.forename: Sergey Vasil'evich
authors.initials: SV
authors.lastname: Sidorov
authors.affiliation: Department of Molecular Immunology, Federal State Budgetary Institution "Research Institute of Fundamental and Clinical Immunology", Yadrintsevskaya St. 14, Novosibirsk, Novosibirsk, Russia, 630099.
authors.forename: Alexander Alexandrovich
authors.initials: AA
authors.lastname: Khristin
authors.affiliation: Vaccine Department, Avaxis Biotherapeutics LLC, Technopark St. 1 116, Koltsovo, Novosibirsk Region, Russia, 630559.
authors.forename: Amir Zakievich
authors.initials: AZ
authors.lastname: Maksyutov
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000502:physiology* / Q000637:transplantation; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes
keywords: Breast cancer; Cytotoxicity; DNA constructs; Dendritic cells; Transfection