Tumor-Specific Gene Delivery Using Recombinant Vaccinia Virus in a Rabbit Model of Liver Metastases

Gnant, Michael; Noll, Linda A.; Irvine, Kari R.; Puhlmann, Markus; Terrill, Richard; Alexander, H. Richard; Bartlett, David L.

doi:10.1093/jnci/91.20.1744

Cited by 57 publications

(26 citation statements)

References 28 publications

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“…Futhermore, intravenous administration of the luciferase-expressing recombinant VV led to significantly higher luciferase activity in different tumor models compared to normal tissues assayed. 27,31 In our biodistribution studies, viral recovery from mouse tissues demonstrated that VV-FCU1 was consistently detected in all s.c. tumors whereas other organs remain much less infected. Our measurement of viral infection of organs is done 14 days after injection.…”

Section: Oncolytic Vaccinia Virus Expressing Fcu1 J Foloppe Et Almentioning

confidence: 75%

“…This was demonstrated in numerous tumor models, including murine colon cancer and melanoma, 27 murine and human ovarian tumors 30 and rabbit kidney cancer. 31 Infection and lysis of 100% of the cells in a tumor is difficult to achieve in vivo using oncolytic viruses alone. Therefore, oncolytic viruses are often 'armed' with enzyme-prodrug systems which are capable of exerting a strong bystander effect and which may enhance the oncolytic efficacy of the virus therapy by eliminating uninfected tumor cells.…”

Section: Discussionmentioning

confidence: 99%

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Targeted delivery of a suicide gene to human colorectal tumors by a conditionally replicating vaccinia virus

et al. 2008

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We have generated a thymidine kinase gene-deleted vaccinia virus (VV) (Copenhagen strain) that expressed the fusion suicide gene FCU1 derived from the yeast cytosine deaminase and uracil phosphoribosyltransferase genes. Intratumoral inoculation of this thymidine kinase genedeleted VV encoding FCU1 (VV-FCU1) in the presence of systemically administered prodrug 5-fluorocytosine (5-FC) produced statistically significant reductions in the growth of subcutaneous human colon cancer in nude mice compared with thymidine kinase gene-deleted VV treatments or with control 5-fluorouracil alone. A limitation of prodrug therapies has often been the requirement for the direct injection of the virus into relatively large, accessible tumors. Here we demonstrate vector targeting of tumors growing subcutaneously following systemic administration of VV-FCU1. More importantly we also demonstrate that the systemic injection of VV-FCU1 in nude mice bearing orthotopic liver metastasis of a human colon cancer, with concomitant administration of 5-FC, leads to substantial tumor growth retardation. In conclusion, the insertion of the fusion FCU1 suicide gene potentiates the oncolytic efficiency of the thymidine kinase gene-deleted VV and represents a potentially efficient means for gene therapy of distant metastasis from colon and other cancers.

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Section: Oncolytic Vaccinia Virus Expressing Fcu1 J Foloppe Et Almentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Targeted delivery of a suicide gene to human colorectal tumors by a conditionally replicating vaccinia virus

et al. 2008

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“…It is of interest to compare these properties with the behavior of other gene delivery systems. In the case of viral vectors, there have been three reports of transgene expression in liver metastases and in a distal tumor following systemic administration of a recombinant vaccinia virus 18,19 and a selectively replicating adenovirus. 20 These viral vectors are replication incompetent in normal nondividing cells but can selectively replicate in tumor cells resulting in transgene expression in tumors and antitumoral efficacy.…”

Section: Figure 4 Toxicity Resulting From IV Injection Into Mice Ofmentioning

confidence: 99%

Stabilized plasmid-lipid particles for systemic gene therapy

et al. 2000

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The structure of 'stabilized plasmid-lipid particles' (SPLP) and their properties as systemic gene therapy vectors has been investigated. We show that SPLP can be visualized employing cryo-electron microscopy to be homogeneous particles of diameter 72 ± 5 nm consisting of a lipid bilayer surrounding a core of plasmid DNA. It is also shown that SPLP exhibit long circulation lifetimes (circulation half-life Ͼ6 h) following intravenous (i.v.) injection in a murine tumor model resulting in accumulation of up to 3% of the total injected dose and concomitant reporter gene expression at a distal (hind flank) tumor site. In contrast, i.v. injection of

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“…32 As demonstration of the selectivity and efficiency, we showed that this virus can be injected intravenously or intraperitoneally and be taken up into a subcutaneous tumor, replicate in the tumor, and lead to an antitumor response. 33 This effect is directly related to intratumoral vaccinia replication, and not a bystander inflammatory response.…”

Section: Cancer Gene Therapymentioning

confidence: 96%

Development of a replication-selective, oncolytic poxvirus for the treatment of human cancers

Zeh

Bartlett

2002

Cancer Gene Ther

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Tumor directed gene therapy for the purpose of destroying cancer cells through replicative "oncolysis" or by intratumoral expression of toxic or immunostimulatory genes requires an efficient, tumor targeted vector. Vectors are limited by inefficient replication in vivo, inefficient tumor targeting, and safety concerns. As a unique approach to addressing these limitations, our laboratory has studied poxviruses as tumor selective replicating vectors. The best in vivo antitumor results achieved to date have been with a mutated WR strain of vaccinia virus. The unique advantage of this strain of vaccinia over other vectors currently being explored for this purpose is the efficiency of in vivo replication. Intradermal injection of 10 6 pfu of the wild type ( non -mutated ) vaccinia in non -human primates leads to a 108 cm 2 zone of necrosis in 8 days -directly related to cellular destruction from viral replication. We have mutated the virus through insertional deletion of both the thymidine kinase ( TK ) gene and vaccinia growth factor ( VGF ) gene. The mutant virus no longer causes destruction of normal tissue, but has completely preserved replication efficiency in tumor tissue and can safely be delivered systematically to successfully treat subcutaneous tumors in mice. Plans are now underway for clinical trials.

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Tumor-Specific Gene Delivery Using Recombinant Vaccinia Virus in a Rabbit Model of Liver Metastases

Cited by 57 publications

References 28 publications

Targeted delivery of a suicide gene to human colorectal tumors by a conditionally replicating vaccinia virus

Targeted delivery of a suicide gene to human colorectal tumors by a conditionally replicating vaccinia virus

Stabilized plasmid-lipid particles for systemic gene therapy

Development of a replication-selective, oncolytic poxvirus for the treatment of human cancers

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