title: Generation of dendritic cell-based vaccine using high hydrostatic pressure for non-small cell lung cancer immunotherapy.
abstract: High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)-based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h. Moreover, DC-based HHP lung cancer vaccine showed functional plasticity after transfer into serum-containing media and stimulation with LPS or CD40L after additional 24h. LPS and CD40L stimulation further differentially enhanced the expression of costimulatory molecules and production of IL-12p70. DC-based HHP lung cancer vaccine decreased the number of CD4+CD25+Foxp3+ T regulatory cells and stimulated IFN-γ-producing tumor antigen-specific CD4+ and CD8+ T cells from non-small cell lung cancer (NSCLC) patients. Tumor antigen specific CD8+ and CD4+ T cell responses were detected in NSCLC patient's against a selected tumor antigens expressed by lung cancer cell lines used for the vaccine generation. We also showed for the first time that protein antigen from HHP-killed lung cancer cells is processed and presented by DC to CD8+ T cells. Our results represent important preclinical data for ongoing NSCLC Phase I/II clinical trial using DC-based active cellular immunotherapy (DCVAC/LuCa) in combination with chemotherapy and immune enhancers.
authors.affiliation: SOTIO, Prague, Czech Republic.|Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Nada
authors.initials: N
authors.lastname: Hradilova
authors.affiliation: SOTIO, Prague, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Sadilkova
authors.affiliation: SOTIO, Prague, Czech Republic.|Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Palata
authors.affiliation: Thoracic and Lung Transplantation Division, 3rd Department of Surgery, 1st Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Mysikova
authors.affiliation: Thoracic and Lung Transplantation Division, 3rd Department of Surgery, 1st Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Mrazkova
authors.affiliation: Thoracic and Lung Transplantation Division, 3rd Department of Surgery, 1st Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Robert
authors.initials: R
authors.lastname: Lischke
authors.affiliation: SOTIO, Prague, Czech Republic.|Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Radek
authors.initials: R
authors.lastname: Spisek
authors.affiliation: SOTIO, Prague, Czech Republic.|Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Irena
authors.initials: I
authors.lastname: Adkins
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D006874:Hydrostatic Pressure; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D008175:Lung Neoplasms / Q000628:therapy*
chemical_list: D019496:Cancer Vaccines; D007371:Interferon-gamma