<i>In Vivo</i>Adenovirus-Mediated Gene Transfer of the<i>Escherichia coli</i>Cytosine Deaminase Gene to Human Colon Carcinoma-Derived Tumors Induces Chemosensitivity to 5-Fluorocytosine

Hirschowitz, Edward A.; Ohwada, Akihiko; Pascal, William R.; Russi, Thomas; Crystal, Ronald G.

doi:10.1089/hum.1995.6.8-1055

Cited by 157 publications

(100 citation statements)

References 29 publications

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“…Assay for CD enzymatic activity An enzymatic assay for CD activity was performed as described by Hirschowitz et al, 41 with the exception that the incubation time for the enzymatic conversion of 5-FC into 5-FU was shortened from 24 to 0.5 h. The enzymatic activity was determined by spectrometry.…”

Section: Recombinant Vvmentioning

confidence: 99%

Oncolytic virotherapy for ovarian carcinomatosis using a replication-selective vaccinia virus armed with a yeast cytosine deaminase gene

et al. 2007

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In this study, we assessed the ability of a highly tumor-selective oncolytic vaccinia virus armed with a yeast cytosine deaminase gene to infect and lyse human and murine ovarian tumors both in vitro and in vivo. The virus vvDD-CD could infect, replicate in and effectively lyse both human and mouse ovarian cancer cells in vitro. In two different treatment schedules involving either murine MOSEC or human A2780 ovarian carcinomatosis models, regional delivery of vvDD-CD selectively targeted tumor cells and ovarian tissue, effectively delaying the development of either tumor or ascites and leading to significant survival advantages. Oncolytic virotherapy using vvDD-CD in combination with the prodrug 5-fluorocytosine conferred an additional long-term survival advantage upon tumor-bearing immunocompetent mice. These findings demonstrate that a tumor-selective oncolytic vaccinia combined with gene-directed enzyme prodrug therapy is a highly effective strategy for treating advanced ovarian cancers in both syngeneic mouse and human xenograft models. Given the biological safety, tumor selectivity and oncolytic potency of this armed oncolytic virus, this dual therapy merits further investigation as a promising new treatment for metastatic ovarian cancer.

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Section: Recombinant Vvmentioning

confidence: 99%

Oncolytic virotherapy for ovarian carcinomatosis using a replication-selective vaccinia virus armed with a yeast cytosine deaminase gene

et al. 2007

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“…A major advantage of gene-directed enzyme prodrug therapy with intracellular enzymes such as thymidine kinase or cytosine deaminase is that they do in fact provide bystander killing of nontransduced target cells. 25,26 Nevertheless, ganciclovir and 5-fluorocytosine must diffuse through gap junctions or be released from apoptotic cells to kill bystander cells. 25,27 These relative inefficient processes thus limit the degree of bystander killing that can be achieved.…”

Section: Discussionmentioning

confidence: 99%

Hapten-directed targeting to single-chain antibody receptors

et al. 2004

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Artificial recombinant receptors may be useful for selectively targeting imaging and therapeutic agents to sites of gene expression. To evaluate this approach, we developed transgenes to express highly on cells a single-chain antibody (scFv) against the hapten 4-ethoxymethylene-2-phenyl-2-oxazoline-5-one (phOx). A phOx enzyme conjugate was created by covalently attaching phOx molecules to polyethylene glycol (PEG)-modified b-glucuronidase. Cells expressing phOx scFv but not control scFv receptors were selectively killed after exposure to -glucuronidase derivatized with phOx and PEG (phOx-bG-PEG) and a glucuronide prodrug (phydroxy aniline mustard b-D-glucuronide, HAMG) of p-hydroxyaniline mustard. Targeted activation of HAMG produced bystander killing of receptor-negative cells in mixed populations containing as few as 10% phOx-receptor-positive cells. Functional phOx scFv receptors were stably expressed on B16-F1 melanoma tumors in vivo. Treatment of mice bearing established phOx-receptorpositive tumors with phOx-bG-PEG and HAMG significantly (Pp.0005) suppressed tumor growth as compared with treatment with bG-PEG and HAMG or prodrug alone. phOx was unstable in the serum, suggesting alternative haptens may be more suitable for in vivo applications. Our results show that therapeutic agents can be targeted to artificial hapten receptors in vitro and in vivo. The expression of artificial receptors on target cells may allow preferential delivery of therapeutic or imaging molecules to sites of transgene expression.

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“…115,116,122 To transduce the cytosine deaminase gene effectively to the tumor, an Ad vector was chosen for construction of AdCMV.CD. 123 The AdCMV.CD vector suppressed HT29 cell growth in vitro in the presence of 5-FC in a dose-dependent manner. Infection with the virus, even when as few as 10% of cells expressed the cytosine deaminase gene, was associated with a bystander effect when combined with 5-FC in cell-mixing studies.…”

Section: Application Of Ad Vectors In Cancer Treatmentmentioning

confidence: 96%

Development and application of adenoviral vectors for gene therapy of cancer

Zhang¹

1999

Cancer Gene Ther

164

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For successful gene vaccination and therapy of cancer, it is essential to develop gene delivery vectors that can meet clinical and social requirements. The need for improved vectors was clearly manifested during the peak of the first wave of gene therapy. Adenoviral (Ad) vectors have recently drawn the attention of many of those involved in the field of gene therapy for cancer because of their practical advantages and application potential. Many experiments, innovations, preclinical studies, and clinical trials have generated an overwhelming amount of data and literature concerning this vector system. It is hoped that the comprehensive review presented here, which includes the principles, potential, capacity, and limitations of the current Ad systems, will help to further the rational development of the system. The literature in this article is organized in an attempt to emphasize Ad vector development in the aspects of technical approaches, practical hurdles and strategies to overcome them, significant experimental results, recent advances, future directions, etc. The technical range of this review covers details that are intended to serve as a reference for advanced technical readers and provide a foundation for initiates in the field of Ad vector gene therapy. The material presented here is also intended for nontechnical persons who want to have an overview of the significance and potential of the technology.

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In VivoAdenovirus-Mediated Gene Transfer of theEscherichia coliCytosine Deaminase Gene to Human Colon Carcinoma-Derived Tumors Induces Chemosensitivity to 5-Fluorocytosine

Cited by 157 publications

References 29 publications

Oncolytic virotherapy for ovarian carcinomatosis using a replication-selective vaccinia virus armed with a yeast cytosine deaminase gene

Oncolytic virotherapy for ovarian carcinomatosis using a replication-selective vaccinia virus armed with a yeast cytosine deaminase gene

Hapten-directed targeting to single-chain antibody receptors

Development and application of adenoviral vectors for gene therapy of cancer

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