Attenuated Semliki Forest virus for cancer treatment in dogs: safety assessment in two laboratory Beagles

BMC Veterinary Research

Ari E. Hinkkanen⁵  Markus J. V. Vähä-Koskela³  Akseli Hemminki⁴  Matti Waris¹  Minna Niittykoski⁵  Marjukka O. Anttila²  Janne J. Ruotsalainen⁵  Karoliina P. M. Autio⁴ 

[1] Department of Virology, University of Turku, Turku, 20014, Finland;Finnish Food Safety Authority Evira, Pathology Unit, Mustialankatu 3, Helsinki, 00790, Finland;Institute of Biotechnology, University of Helsinki, Helsinki, 00014, Finland;Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, 00014, Finland;A. I. Virtanen Institute for Molecular Sciences, Biotechnology and Molecular Medicine, University of Eastern Finland, Kuopio, 70211, Finland

关键词: Cancer;    Canine;    Semliki Forest virus;    Oncolytic virus;   

Others  :  1224404
DOI  :  10.1186/s12917-015-0498-2

 received in 2015-02-25, accepted in 2015-07-20,  发布年份 2015

【 摘 要 】

Background

Dogs suffer from spontaneous tumors which may be amenable to therapies developed for human cancer patients, and dogs may serve as large-animal cancer models. A non-pathogenic Semliki Forest virus vector VA7-EGFP previously showed promise in targeting human tumor xenografts in mice, but the oncolytic capacity of the virus in canine cancer cells and the safety of the virus in higher mammals such as dogs, are not known. We therefore assessed the oncolytic potency of VA7-EGFP against canine cancer cells by infectivity and viability assays in two dog solid tumor cell lines. Furthermore we performed a 3-week safety study in two adult Beagles which received a single intravenous injection of ~2 × 10 ⁵plaque forming units of parental A7(74) strain.

Results

VA7-EGFP was able to replicate in and kill both canine cancer cell lines tested. No adverse events were observed in either of the two virus-injected adult Beagles and no infective virus could be recovered from any of the biological samples collected over the course of the study. Neutralizing antibodies to Semliki Forest virus became detectable in the dogs at 5 days post infection and remained elevated until study termination.

Conclusions

Based on these results, testing of the oncolytic potential of attenuated Semliki Forest virus in canine cancer patients appears feasible.

【 授权许可】

   
2015 Autio et al.

【 图 表 】

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