Immunosuppression promotes reovirus therapy of colorectal liver metastases.

Abstract:

:Mortality due to colorectal cancer (CRC) is high and is associated with the development of liver metastases. Approximately 40% of human CRCs harbor an activating mutation in the KRAS oncogene. Tumor cells with activated KRAS are particularly sensitive to Reovirus T3D, a non-pathogenic oncolytic virus. The efficacy of virus-based therapies may be positively or negatively modulated by the host immune system. This study was designed to assess the effect of immunosuppression on Reovirus T3D oncolysis of established colorectal micrometastases in the liver. Mouse C26 CRC cells harbor a mutant Kras gene and are susceptible to Kras-dependent oncolysis by Reovirus T3D in vitro. Isolated C26 liver tumors were established in syngenic immunocompetent BALB/c mice by intrahepatic injection. Reovirus T3D therapy was given as a single intratumoral injection in control mice and in cyclosporin A-treated immunosuppressed mice. Tumor growth was analyzed over time by non-invasive bioluminescence imaging. The outgrowth of established CRC liver metastases in immunocompetent mice was efficiently but temporarily inhibited with a single injection of Reovirus T3D. Immunosuppression with cyclosporin A markedly increased and prolonged the therapeutic effect and allowed complete Reovirus T3D-induced tumor eradication in a subpopulation of the mice. We conclude that Reovirus T3D is an effective therapeutic agent against established C26 colorectal liver metastases and that immunosuppression enhances treatment efficacy. Cancer Gene Therapy (2006) 13, 815-818. doi:10.1038/sj.cgt.7700949; published online 10 March 2006.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Smakman N,van der Bilt JD,van den Wollenberg DJ,Hoeben RC,Borel Rinkes IH,Kranenburg O

doi

10.1038/sj.cgt.7700949

subject

Has Abstract

pub_date

2006-08-01 00:00:00

pages

815-8

issue

8

eissn

0929-1903

issn

1476-5500

pii

7700949

journal_volume

13

pub_type

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