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National Repository of Grey Literature

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Non-small cell lung cancer immunotherapy based on dendritic cell vaccine pulsed with tumor cells killed by immunogenic cell death Podzimková, Naďa ; Adkins, Irena (advisor) ; Ryška, Aleš (referee) ; Froňková, Eva (referee) Lung carcinoma represents the leading cause of cancer mortality worldwide with dismal prognosis. Immunotherapy exploiting the patient's own immune system is booming along with dendritic cell (DC)-based immunotherapy in recent years. The use of DC-based vaccines for treatment of non-small cell lung cancer is, however, still limited with limited clinical efficacy despite the development of various techniques for the vaccine preparation. In this study, we focused on the development and characterization of DC-based vaccine pulsed with multi-antigenic tumor cells killed with high hydrostatic pressure (HHP) and cytotoxic hyperthermia (cHT). Both physical modalities induced immunogenic cell death which leads to DC activation and more efficient onset of antitumor immunity. The molecular apoptotic pathways activated upon HHP and cHT treatment in tumor cells were analyzed and the optimal conditions to achieve high mortality, high immunogenicity and low antigen degradation were identified. We also showed that the prophylactic vaccination of mice with cHT-treated tumor cells significantly delayed tumor growth and prolonged mice survival. DC pulsed with HHP or cHT-treated tumor cells exhibited phenotypic maturation, increased chemotactic migration, higher production of proinflammatory cytokines and increased... Detailed record

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