Tumor-Selective Gene Expression in a Hepatic Metastasis Model after Locoregional Delivery of a Replication-Competent Retrovirus Vector

Purpose: Replication-competent retrovirus (RCR) vectors have been shown to achieve highly efficient and tumor-restricted replicative spread and gene transfer in vivo after direct intratumoral injection in a variety of primary cancer models. In this setting, the intrinsic inability of retroviruses to...

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Bibliographic Details
Published in:Clinical cancer research 2006-12, Vol.12 (23), p.7108-7116
Main Authors: HIRAOKA, Kei, KIMURA, Takahiro, LOGG, Christopher R, KASAHARA, Noriyuki
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Animals
Antineoplastic agents
Biological and medical sciences
Catheterization - methods
Cell Line, Tumor
colon cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - therapy
Colorectal Neoplasms - virology
Disease Models, Animal
Female
Gastroenterology. Liver. Pancreas. Abdomen
Gene Expression Profiling
gene therapy
Genetic Therapy - methods
Genetic Vectors - administration & dosage
Genetic Vectors - genetics
Humans
Infusions, Intralesional
liver metastasis
Liver Neoplasms, Experimental - genetics
Liver Neoplasms, Experimental - secondary
Liver Neoplasms, Experimental - therapy
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Mice
Mice, Nude
molecular imaging
oncolytic virotherapy
Pharmacology. Drug treatments
Predictive Value of Tests
retrovirus
Reverse Transcriptase Polymerase Chain Reaction - methods
Transfection
Transplantation, Heterologous
Tumors
Virus Replication
Xenograft Model Antitumor Assays
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Summary:Purpose: Replication-competent retrovirus (RCR) vectors have been shown to achieve highly efficient and tumor-restricted replicative spread and gene transfer in vivo after direct intratumoral injection in a variety of primary cancer models. In this setting, the intrinsic inability of retroviruses to infect postmitotic normal cells, combined with their unique ability to persist through stable integration, allow further transduction of ectopic tumor foci as the infected cancer cells migrate. However, i.v. delivery of RCR vectors has never been tested previously, particularly in an immunocompetent tumor model. Experimental Design: We combined optical imaging, flow cytometry, and molecular analysis to monitor RCR vector spread after administration via locoregional infusion in a hepatic metastasis model of colorectal cancer. Results: Robust RCR replication was first confirmed in both human WiDr and murine CT26 colorectal cancer cells in vitro , with transduction levels reaching >90% in
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-06-1452