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Oncolytic vesicular stomatitis virus administered by isolated limb perfusion suppresses osteosarcoma growth
Author(s) -
Kubo Tadahiko,
Shimose Shoji,
Matsuo Toshihiro,
Fujimori Jun,
Sakaguchi Takemasa,
Yamaki Minoru,
Shinozaki Katsunori,
Woo Savio L.C.,
Ochi Mitsuo
Publication year - 2011
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21307
Subject(s) - oncolytic virus , vesicular stomatitis virus , osteosarcoma , cancer research , virus , stromal cell , sarcoma , genetic enhancement , virology , medicine , biology , immunology , pathology , gene , biochemistry
A significant limitation to oncolytic virotherapy in vivo is the lack of a clinically relevant means of delivering the virus. We evaluated the oncolytic activity of vesicular stomatitis virus (VSV) in human osteosarcoma cells and explored isolated limb perfusion (ILP) as a novel oncolytic virus delivery system to extremity sarcoma in immune‐competent rats. Human and rat osteosarcoma cells transduced with rVSV‐lacZ uniformly expressed β‐gal. VSV was fully capable of replicating its RNA genome in all osteosarcoma cell lines, and efficiently killed them in time‐ and dose‐dependent manners, whereas normal bone marrow stromal cells were refractory to the virus. VSV delivered by ILP inhibited growth of osteosarcoma xenografts more potently than that injected intravenously and intratumorally in the hind limb of immune‐competent rats. Histopathological sections of tumor lesions treated by ILP‐delivered VSV showed positive for VSV‐G protein. There were no VSV‐G expressions in perfused leg muscle, nonperfused leg muscle, brain, lung, and liver in VSV‐treated rats. Our findings show efficient VSV gene expression and replication in osteosarcoma cells, suggesting that osteosarcoma may be a promising target for oncolytic virotherapy with VSV. Furthermore, we firstly showed that ILP of VSV against extremity sarcoma caused antitumor activity. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:795–800, 2011