Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma

Rampling, Roy; Cruickshank, Garth; Papanastassiou, Vakis; Nicoll, James; Hadley, Donald M.; Brennan, David; Petty, Richard; Maclean, Alasdair; Harland, J; McKie, Elizabeth A.; Mabbs, R; Brown, Maureen D.

doi:10.1038/sj.gt.3301184

Cited by 548 publications

(360 citation statements)

References 28 publications

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“…therapy including the oncolytic vectors that are currently on clinical trials 47,48 express ICP0 and ICP4 genes, the potential risk of deregulation of gene expression in infected normal cells should be considered. In the case of oncolytic HSV-1 vectors, the risk of adverse deregulation in host cells may not pose a significant problem since the duration of the viral IE gene expression is short.…”

Section: Hsv-1 Upregulates Telomerase C-t Yang Et Almentioning

confidence: 99%

“…48,64,65 While the safety concern for viral vectors has been concentrated to virus-induced lytic toxicity. 48,[66][67][68] our present study alerts to the potential risk of oncogenesis through deregulation of host gene expression in normal cells. It is not unreasonable to predict that nonherpes viral vectors may have similar effects on host cells.…”

Section: Hsv-1 Upregulates Telomerase C-t Yang Et Almentioning

confidence: 99%

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Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

Yang

Song

et al. 2003

Gene Ther

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Section: Hsv-1 Upregulates Telomerase C-t Yang Et Almentioning

confidence: 99%

Section: Hsv-1 Upregulates Telomerase C-t Yang Et Almentioning

confidence: 99%

Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

Yang

Song

et al. 2003

Gene Ther

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“…5,6 ICP34.5 deletion mutants cannot replicate in terminally differentiated cells but will lytically infect dividing cells and this has proved to be an effective tumour destruction strategy. In recent clinical trials, injection of HSV1716 has been shown to be safe in treating patients with recurrent glioma, metastatic melanoma and squamous cell carcinoma of the head and neck 7 and proof of principle of selective replication within tumours has been obtained. [8][9][10][11] An essential strategy for the improved effectiveness of oncolytic viral therapies depends upon systemic delivery of targeted viruses that seek out and destroy all cancerous cells.…”

Section: Introductionmentioning

confidence: 99%

A strategy for systemic delivery of the oncolytic herpes virus HSV1716: redirected tropism by antibody-binding sites incorporated on the virion surface as a glycoprotein D fusion protein

2008

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We report on the ability of single-chain variable fragment (scFv) incorporated into the viral envelope to alter the tropism of herpes simplex virus (HSV) 1716. Using recombinant viruses expressing fusion proteins comprising cellsurface antigen-specific scFvs N terminus linked to amino acids 274-393 of gD, we demonstrated that the tropism of these HSV1716 variants was modified such that infection was mediated by the cognate antigen. Thus, an HSV1716 variant that expressed an anti-CD55 scFv targeting moiety linked to these gD residues was able to infect non-permissive Chinese hamster ovary cells expressing CD55 and this infection was specifically blocked by an anti-CD55 monoclonal antibody. Similarly, the infection efficiency of an HSV1716 variant for semi-permissive human leukaemic, CD38-positive cell lines was greatly improved by an anti-CD38 scFv targeting moiety linked to gD residues 274-393, and this enhanced infectivity was abrogated specifically by an anti-CD38 monoclonal antibody. Finally, intravenous/ intraperitoneal injection of an HSV1716 variant displaying an anti-epidermal growth factor receptor (EGFR) scFv linked to residues 274-393 of gD enhanced destruction of subcutaneous EGFR-positive tumours in nude mice compared to unmodified HSV1716. Therefore, targeting of HSV1716 oncolysis to specific cell types through the display of entry mediating scFv/gD fusion proteins represents an efficient route for systemic delivery.

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“…[18][19][20][21][22][23] Several ongoing human clinical trials are based on HSV vectors. [24][25][26] One of the two broad categories of HSV-based vectors, the amplicon, is a plasmid-type vector, which carries an HSV-1 lytic replication origin (ori s ) and HSV-1 packaging signal sequence. The amplicon can be amplified and packaged into infectious HSV-1 virions in the presence of the helper virus.…”

Section: Introductionmentioning

confidence: 99%

Functional expression of ATM gene carried by HSV amplicon vector in vitro and in vivo

Shackelford

Manuszak

et al. 2003

Gene Ther

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Ataxia-telangiectasia (AT) is a human autosomal recessive disease with a pleiotropic phenotype characterized by cerebellar degeneration, immunodeficiency, premature aging, cancer predisposition, and radiation sensitivity. The gene mutated in AT, ATM (for AT-mutated), had been cloned and found to have ionizing radiation and oxidative stressinducible kinase activity. No treatment can stop the progression of the disease. In this study, the complete open-reading frame of ATM cDNA was cloned into a Herpes simplex virus type-1 (HSV-1) amplicon vector (pTO-ATM), and the transduction of cultured AT cells was demonstrated by immunohistochemistry and Western blot analysis. Functional gene expression was evaluated by cell colony-forming assays following exposure to oxidative stress. The survival of AT cells with ATM gene transduction was about 100% higher compared to nontransduced cells after t-butyl hydroperoxide treatments. Next, the normal ATM gene expression in different regions of the rat brain was studied. Immunohistochemistry staining demonstrated weak endogenous ATM protein expression in neurons of the caudate-putamen, with significantly higher levels of expression detected in neurons in other brain regions. Exogenous ATM gene expression from pTO-ATM after viral transduction in the caudateputamen of the adult rat was examined. At 3 days after injection of the pTO-ATM viral vector, abundant positive ATM staining of the neurons was found at the injection sites, in comparison to the controls. These data demonstrate that the relatively large ATM cDNA can be transduced and expressed in vitro and in vivo from an HSV amplicon viral vector. These data provide initial evidence that the replacement of the ATM gene into the cells of AT patients might be possible some day.

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Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma

Cited by 548 publications

References 28 publications

Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

A strategy for systemic delivery of the oncolytic herpes virus HSV1716: redirected tropism by antibody-binding sites incorporated on the virion surface as a glycoprotein D fusion protein

Functional expression of ATM gene carried by HSV amplicon vector in vitro and in vivo

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