The oncolytic effect in vivo of reovirus on tumour cells that have survived reovirus cell killing in vitro

The use of oncolytic viruses has received considerable attention in recent years and many viruses have proved to be effective against a variety of cancer models and a few are currently being used in clinical trials. However, the possible emergence and outcome of virus-resistant tumour cells has not...

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Bibliographic Details
Published in:British journal of cancer 2006-10, Vol.95 (8), p.1020-1027
Main Authors: ALAIN, T, KIM, M, JOHNSTON, R. N, URBANSKI, S, KOSSAKOWSKA, A. E, FORSYTH, P. A, LEE, P. W. K
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Burkitt Lymphoma - pathology
Burkitt Lymphoma - therapy
Burkitt Lymphoma - virology
Cancer research
Cell Line, Tumor
Cell Survival - drug effects
Cell Survival - physiology
Clinical trials
Cysteine Proteinase Inhibitors - pharmacology
Humans
Infections
Leucine - analogs & derivatives
Leucine - pharmacology
Lymphoma
Mammalian orthoreovirus 3 - drug effects
Mammalian orthoreovirus 3 - physiology
Medical research
Medical sciences
Mice
Mice, SCID
Oncolytic Virotherapy
Oncolytic Viruses - drug effects
Oncolytic Viruses - physiology
Reovirus
Time Factors
Translational Therapeutics
Tumors
Viral infections
Virion - drug effects
Virion - physiology
Viruses
Xenograft Model Antitumor Assays
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Summary:The use of oncolytic viruses has received considerable attention in recent years and many viruses have proved to be effective against a variety of cancer models and a few are currently being used in clinical trials. However, the possible emergence and outcome of virus-resistant tumour cells has not been addressed. We previously reported the effective use of reovirus against lymphoid malignancies, including the Burkitt's lymphoma cell line Raji. Here we isolated in vitro persistently infected (PI) Raji cells, and cells 'cured' of persistent reovirus infection ('cured' cells). Both PI and cured Raji cells resisted reovirus infection and cell killing in vitro. In vivo, the PI cells were non-tumorigenic in SCID mice, but cured cells regained the parental cells' ability to form tumours. Tumour xenografts from the cured cells, however, were highly susceptible to reovirus oncolysis in vivo. This susceptibility was due to the proteolytic environment within tumours that facilitates reovirus infection and cell killing. Our results show that persistent infection by reovirus impedes tumour development and that although PI cells cleared of reovirus are tumorigenic, they are killed upon rechallenge with reovirus. Both the PI and cured states are therefore not likely to be significant barriers to reovirus oncolytic therapy.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6603363