Resumen
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.
Idioma original | English |
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Páginas (desde-hasta) | 290-299 |
Número de páginas | 10 |
Publicación | British Journal of Cancer |
Volumen | 104 |
N.º | 2 |
DOI | |
Estado | Published - ene. 18 2011 |
Nota bibliográfica
Funding Information:This work was completed as part of a PhD thesis by MK. This work was supported by grants from the Canadian Institutes of Health Research (to RNJ and PWKL), the Canadian Breast Cancer Foundation (to RNJ), the National Cancer Institute of Canada (to PF), the Terry Fox Foundation (PWKL) and the Alberta Cancer Board (to RNJ and DER). NzN and KG were funded by the Alberta Heritage Foundation for Medical Research and the National Science and Engineering Research Council of Canada, respectively. TA was supported by the Canadian Institutes for Health Research and by the Alberta Heritage Foundation for Medical Research. We also would like to acknowledge Eileen Rattner, who derived the MES1 ESC line, and Laurie Robertson, who operated the Flow Cytometry Core Facility at the University of Calgary.
ASJC Scopus Subject Areas
- Oncology
- Cancer Research
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't