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

JOURNAL OF CONTROLLED RELEASE

卷:283

Article

Garofalo, M.^1,2,3  Saari, H.^1,2  Somersalo, P.^1,2,3  Crescenti, D.³  Kuryk, L.^1,2,4,5  Aksela, L.^1,2  Capasso, C.⁶  Madetoja, M.⁷  Koskinen, K.⁸  Oksanen, T.^1,2  Makitie, A.^9,10  Jalasvuori, M.^1,2,8  Cerullo, V.⁶  Ciana, P.³  Yliperttula, M.^1,2 

[1] Univ Helsinki, Div Pharmaceut Biosci, Viikinkaari 5, Helsinki 00790, Finland

[2] Univ Helsinki, Ctr Drug Res, Viikinkaari 5, Helsinki 00790, Finland

[3] Univ Milan, Ctr Excellence Neurodegenerat Dis, Dept Oncol & Hematooncol, Via Balzaretti 9, I-20133 Milan, Italy

[4] Natl Inst Hyg, Natl Inst Publ Hlth, Dept Virol, 24 Chocimska Str, PL-00791 Warsaw, Poland

[5] Targovax Oy, R&D, Clin Sci, Saukonpaadenranta 2, Helsinki 00180, Finland

[6] Univ Helsinki, Fac Pharm, Drug Res Program, Lab ImmunoViroTherapy, Viikinkaari 5, Helsinki 00790, Finland

[7] Made Consulting, Tykistokatu 4 B, FI-20520 Turku, Finland

[8] Univ Jyvaskyla, Nanosci Ctr, Biol & Environm Sci, Survontie 9C, Jyvaskyla 40500, Finland

[9] Helsinki Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, POB 263, FI-00029 Helsinki, Finland

[10] Univ Helsinki, POB 263, FI-00029 Helsinki, Finland

关键词: Extracellular vesicles;    Oncolytic viruses;    Cancer therapy;    Drug delivery;    Paclitaxel;    Xenograft animal model;    Lung cancer;   

DOI  :  10.1016/j.jconrel.2018.05.015

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free