Double‐deleted vaccinia virus in virotherapy for refractory and metastatic pediatric solid tumors

Molecular Oncology - Tập 7 - Trang 944-954 - 2013
Xueqing Lun1, Yibing Ruan1, Aarthi Jayanthan1, David J. Liu1, Anjali Singh1, Tanya Trippett1,2, John Bell3, Peter Forsyth4, Randal N. Johnston5, Aru Narendran1
1Pediatric Oncology Experimental Therapeutics Investigators Consortium (POETIC) Laboratory for Pre-Clinical and Drug Discovery Studies, University of Calgary, Canada and Division of Pediatric Oncology, Alberta Children's Hospital, Calgary, Alberta, Canada
2Memorial Sloan Kettering Cancer Center, New York, NY, USA
3Ottawa Regional Cancer Centre Research Laboratories, Ottawa, Ontario, Canada
4Moffitt Cancer Center & Research Institute and University of Southern Florida, Tampa, FL, USA
5Department of Biochemistry & Molecular Biology, Faculty of Medicine, University of Calgary, Alberta, Canada

Tóm tắt

BackgroundPrevious studies have shown successful antitumor effects of systemically delivered double‐deleted vaccinia virus (vvDD) against a number of adult tumor models, including glioma, colon and ovarian cancers. The purpose of this study was to investigate the oncolytic potential of vvDD against a panel of cell lines representative of pediatric solid tumors that are currently difficult to cure.MethodsCell lines derived from central nervous system atypical teratoid rhabdoid tumor (AT/RT) (BT12, BT16 and KCCF1), sarcoma (143B, HOS, RD and RH30), and neuroblastoma (SKNAS, SKNBE2, IMR‐5 and IMR‐32) were examined for vvDD mediated cytotoxicity defined by virus expansion followed by loss of tumor cell viability. The normal human fibroblast cell line HS68 was used as a control. Next, relevant orthotopic, subcutaneous and lung metastasis xenograft models were treated with intravenous doses of live vvDD or killed virus controls (DV). Tumor growth inhibition and viral replication were quantified and survival outcomes of these animals were assessed.ResultsvvDD was able to infect and kill nine of eleven of the pediatric tumor cells (81.8%) in vitro. In xenograft models, intravenous administration of a single dose of vvDD significantly inhibited the growth of tumors and prolonged the survival of intracranial and metastatic tumors.ConclusionsOncolytic vvDD administered i.v. shows activity in preclinical models of pediatric malignancies that are resistant to many currently available treatments. Our data support further evaluation of vvDD virotherapy for refractory pediatric solid tumors.

Tài liệu tham khảo

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Molecular Oncology

Tập 7

944-954

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