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Attenuated reovirus displays oncolysis with reduced host toxicity

 
: Kim, Mimi; Garant, Katy A.; Nieden, Nicole zur; Alain, Tommy; Loken, Steven D.; Urbanski, Stefan J.; Forsyth, Peter A.; Rancourt, Derrick; Lee, Patrick W.; Johnston, Randal N.

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The British journal of cancer 104 (2011), No.2, pp.290-299
ISSN: 0007-0920
English
Journal Article
Fraunhofer IZI ()
mammalian reovirus; attenuated; persistent infection; oncolysis; reduced toxicity; sigma1

Abstract
Background:
Although the naturally occurring reovirus causes only mild symptoms in humans, it shows considerable potential as an oncolytic agent because of its innate ability to target cancer cells. In immunocompromised hosts, however, wild-type reovirus can target healthy tissues, including heart, liver, pancreas and neural structures.
Methods:
We characterized an attenuated form of reovirus (AV) derived from a persistently infected cell line through sequence analysis, as well as western blot and in vitro transcription and translation techniques. To examine its pathogenesis and oncolytic potential, AV reovirus was tested on healthy embryonic stem cells, various non-transformed and transformed cell lines, and in severe combined immunodeficiency (SCID) mice with tumour xenografts.
Results:
Sequence analysis of AV reovirus revealed a premature STOP codon in its sigma 1 attachment protein. Western blot and in vitro translation confirmed the presence of a truncated ?1. In comparison to wild-type reovirus, AV reovirus did not kill healthy stem cells or induce black tail formation in SCID mice. However, it did retain its ability to target cancer cells and reduce tumour size.
Conclusion:
Despite containing a truncated attachment protein, AV reovirus still preferentially targets cancer cells, and compared with wild-type reovirus it shows reduced toxicity when administered to immunodeficient hosts, suggesting the potential use of AV reovirus in combination cancer therapy.

: http://publica.fraunhofer.de/documents/N-192792.html