Combined HSV-1 recombinant and amplicon piggyback vectors: replication-competent and defective forms, and therapeutic efficacy for experimental gliomas

Pecháň, Peter; Herrlinger, Ulrich; Aghi, Manish K.; Breakefield, Xandra O.

doi:10.1002/(sici)1521-2254(199905/06)1:3<176::aid-jgm35>3.0.co;2-t

Cited by 16 publications

(5 citation statements)

References 30 publications

(31 reference statements)

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“…31 These include acute cytopathic effects induced by the helper virus, reversion of the helper virus to wt-HSV-1 phenotype by recombination and unreliability of transgene expression. Therefore, helper virus-free packaging systems were developed using replicationcompetent, packaging-defective genomes of HSV-1 to provide the functions necessary for replication and packaging of cotransfected amplicon DNA.…”

Section: Discussionmentioning

confidence: 99%

Variability in infectivity of primary cell cultures of human brain tumors with HSV-1 amplicon vectors

et al. 2005

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We investigated the variability in infectivity of cells in primary brain tumor samples from different patients using an HSV-1 amplicon vector. We studied the infectivity of HSV-1 amplicon vectors in tumor samples derived from neurosurgical resections of 20 patients. Cells were infected with a definite amount of HSV-1 amplicon vector HSV-GFP. Transduction efficiency in primary tumor cell cultures was compared to an established human glioma line. Moreover, duration of transgene expression was monitored in different tumor cell types. All primary cell cultures were infectable with HSV-GFP with variable transduction efficiencies ranging between 3.0 and 42.4% from reference human Gli36DEGFR glioma cells. Transduction efficiency was significantly greater in anaplastic gliomas and meningiomas (26.7717.4%) compared to more malignant tumor types (glioblastomas, metastases; 11.278.5%; P ¼ 0.05). To further investigate the possible underlying mechanism of this variability, nectin-1/HevC expression was analyzed and was found to contribute, at least in part, to this variability in infectability. The tumor cells expressed the exogenous gene for 7 to 61 days with significant shorter expression in glioblastomas (18713 d) compared to anaplastic gliomas (42724 d; Po0.05). Interindividual variability of infectivity by HSV-1 virions might explain, at least in part, why some patients enrolled in gene therapy for glioblastoma in the past exhibited a sustained response to HSV-1-based gene-and virus therapy. Infectivity of primary tumor samples from respective patients should be tested to enable the development of efficient and safe herpes vector-based gene and virus therapy for clinical application. Gene Therapy (2005) 12, 588-596.

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Section: Discussionmentioning

confidence: 99%

Variability in infectivity of primary cell cultures of human brain tumors with HSV-1 amplicon vectors

et al. 2005

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“…HSV‐1 vectors comprise two types: (1) recombinant virus vectors, including two subtypes (a) replication‐conditional vectors (for review see Andreansky et al ., 1996; Herrlinger et al ., 2000; Martuza et al ., 199135–37), which are mutated in genes involved in nucleoside metabolism allowing replication only in dividing cells, i.e. tumor cells in the brain, and (b) replication‐defective vectors, which are mutated in genes essential for virus replication5, 38; and (2) amplicon vectors39–41, which are DNA plasmids bearing the HSV‐1 origin of DNA replication (ori S ) and packaging signal (pac), as well as transgenes, packaged in HSV‐1 virions. Packaging of amplicon vectors depends on HSV‐1 helper functions which can be provided by replication‐defective virus in cells complementing the defect42 or by pac‐deleted HSV‐1 DNA in cosmids43 or F plasmids44, 45.…”

Section: Introductionmentioning

confidence: 99%

HSV-1 infected cell proteins influence tetracycline-regulated transgene expression

et al. 2000

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“…44,57 -59 In addition, another new hybrid HSV /AAV amplicon vector system was created that may allow long -term transgene expression in brain and liver helper virus. 43,60,61 Finally, replication-competent herpes vectors under development may prove superior to replicationincompetent systems like ours. 62 The cytopathic replication -competent effects of modified HSV-1 viruses and their derived vectors can be used to excellent advantage against tumor cells.…”

Section: Discussionmentioning

confidence: 90%

Antitumor effects on human melanoma xenografts of an amplicon vector transducing the herpes thymidine kinase gene followed by ganciclovir

Wang

Smith

et al. 2002

Cancer Gene Ther

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Herpes simplex virus type-1 (HSV-1) has been demonstrated as a potentially useful gene delivery vector for gene therapy due to its high efficiency of in vivo transduction. The helper virus-dependent, HSV- 1 amplicon vectors were developed for easier operation and their larger capacity. In this study, the herpes simplex virus type-1 thymidine kinase (HSVtk) gene was cloned into the pHE700 amplicon vector to make an HE7tk vector and used for in vivo gene delivery. Human melanoma xenografts were established in athymic nude mice. Tumors were injected directly with HE7tk vector alone, HE7tk vector followed by ganciclovir (GCV), or a pHE700 amplicon vector carrying a green fluorescent protein (HE7GFP) gene followed by GCV. Efficient HSVtk transgene expression was found in the tumor 3 days after injection. Animals transduced with HE7tk followed by GCV had minimal tumor growth (P < .01 ). Animals that received either HE7tk vector without GCV or HE7GFP vector with GCV had some reduction in tumor growth compared to animals that were injected with buffer only. These data indicate that replication-defective HSV-1 amplicon vectors can be used effectively to deliver transgenes into solid tumors in vivo.

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Combined HSV-1 recombinant and amplicon piggyback vectors: replication-competent and defective forms, and therapeutic efficacy for experimental gliomas

Cited by 16 publications

References 30 publications

Variability in infectivity of primary cell cultures of human brain tumors with HSV-1 amplicon vectors

Variability in infectivity of primary cell cultures of human brain tumors with HSV-1 amplicon vectors

HSV-1 infected cell proteins influence tetracycline-regulated transgene expression

Antitumor effects on human melanoma xenografts of an amplicon vector transducing the herpes thymidine kinase gene followed by ganciclovir

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