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

Abstract:

: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.

journal_name

Br J Cancer

authors

Alain T,Kim M,Johnston RN,Urbanski S,Kossakowska AE,Forsyth PA,Lee PW

doi

10.1038/sj.bjc.6603363

subject

Has Abstract

pub_date

2006-10-23 00:00:00

pages

1020-7

issue

8

eissn

0007-0920

issn

1532-1827

pii

6603363

journal_volume

95

pub_type

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