Antitumor effect of oncolytic virus and paclitaxel encapsulated in extracellular vesicles for lung cancer treatment

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Garofalo , M , Saari , H , Somersalo , P , Crescenti , D , Kuryk , L , Aksela , L , Capasso , C , Madetoja , M , Koskinen , K , Oksanen , T , Mäkitie , A , Jalasvuori , M , Cerullo , V , Ciana , P & Yliperttula , M 2018 , ' Antitumor effect of oncolytic virus and paclitaxel encapsulated in extracellular vesicles for lung cancer treatment ' , Journal of Controlled Release , vol. 283 , pp. 223-234 . https://doi.org/10.1016/j.jconrel.2018.05.015

Title: Antitumor effect of oncolytic virus and paclitaxel encapsulated in extracellular vesicles for lung cancer treatment
Author: Garofalo, M.; Saari, H.; Somersalo, P.; Crescenti, D.; Kuryk, L.; Aksela, L.; Capasso, C.; Madetoja, M.; Koskinen, K.; Oksanen, T.; Mäkitie, A.; Jalasvuori, M.; Cerullo, V.; Ciana, P.; Yliperttula, M.
Other contributor: University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Clinicum
University of Helsinki, Drug Research Program
University of Helsinki, Drug Research Program







Date: 2018-08-10
Language: eng
Number of pages: 12
Belongs to series: Journal of Controlled Release
ISSN: 0168-3659
DOI: https://doi.org/10.1016/j.jconrel.2018.05.015
URI: http://hdl.handle.net/10138/237272
Abstract: Standard of care for cancer is commonly a combination of surgery with radiotherapy or chemoradiotherapy. However, in some advanced cancer patients this approach might still remaininefficient and may cause many side effects, including severe complications and even death. Oncolytic viruses exhibit different anti-cancer mechanisms compared with conventional therapies, allowing the possibility for improved effect in cancer therapy. Chemotherapeutics combined with oncolytic viruses exhibit stronger cytotoxic responses and oncolysis. Here, we have investigated the systemic delivery of the oncolytic adenovirus and paclitaxel encapsulated in extracellular vesicles (EV) formulation that, in vitro, significantly increased the transduction ratio and the infectious titer when compared with the virus and paclitaxel alone. We demonstrated that the obtained EV formulation reduced the in vivo tumor growth in animal xenograft model of human lung cancer. Indeed, we found that combined treatment of oncolytic adenovirus and paclitaxel encapsulated in EV has enhanced anticancer effects both in vitro and in vivo in lung cancer models. Transcriptomic comparison carried out on the explanted xenografts from the different treatment groups revealed that only 5.3% of the differentially expressed genes were overlapping indicating that a de novo genetic program is triggered by the presence of the encapsulated paclitaxel: this novel genetic program might be responsible of the observed enhanced antitumor effect. Our work provides a promising approach combining anticancer drugs and viral therapies by intravenous EV delivery as a strategy for the lung cancer treatment.
Subject: 3122 Cancers
317 Pharmacy
Extracellular vesicles
Oncolytic viruses
Cancer therapy
Drug delivery
Paclitaxel
Xenograft animal model
Lung cancer
CELLS
OVARIAN-CANCER
MODEL
CHEMOTHERAPY
ENDOSTATIN
VIROTHERAPY
GENE
ADENOVIRUS RECEPTOR
EFFICIENCY
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