Antitumor effect of oncolytic virus and paclitaxel encapsulated in extracellular vesicles for lung cancer treatment
| Autor: | Daniela Crescenti, Heikki Saari, Timo Oksanen, Paolo Ciana, Marjo Yliperttula, Antti Mäkitie, Katariina Koskinen, Mariangela Garofalo, Matti Jalasvuori, Lukasz Kuryk, Mari Madetoja, Petter Somersalo, Vincenzo Cerullo, Cristian Capasso, L. Aksela |
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| Přispěvatelé: | Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, ImmunoViroTherapy Lab, Clinicum, Korva-, nenä- ja kurkkutautien klinikka, Drug Research Program, Biopharmaceutics Group |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Lung Neoplasms Cancer therapy medicine.medical_treatment Pharmaceutical Science Oncolytic viruses chemistry.chemical_compound paclitaxel keuhkosyöpä 0302 clinical medicine Medicine Mice Inbred BALB C Extracellular vesicles CHEMOTHERAPY Combined Modality Therapy 3. Good health xenograft animal model Paclitaxel Liver 317 Pharmacy 030220 oncology & carcinogenesis onkolyyttiset virukset cancer therapy Female Lung cancer onkolyyttinen virushoito Oncolytic adenovirus EFFICIENCY Drug delivery Xenograft animal model 3003 3122 Cancers Mice Nude ta3111 OVARIAN-CANCER VIROTHERAPY 03 medical and health sciences Cell Line Tumor Animals Humans Virotherapy Chemotherapy ADENOVIRUS RECEPTOR syöpähoidot business.industry ta1182 Cancer ENDOSTATIN medicine.disease ta3122 Antineoplastic Agents Phytogenic GENE Oncolytic virus MODEL lung cancer 030104 developmental biology chemistry viroterapia CELLS drug delivery Cancer research business Ovarian cancer solunulkoiset vesikkelit Spleen |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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