G207, modified herpes simplex virus type 1, kills human pancreatic cancer cells in vitro

Lee, Jonathan H.; Federoff, Howard J.; Schoeniger, Luke O.

doi:10.1016/s1091-255x(99)80021-3

Cited by 21 publications

(9 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DOI: 10.1038/sj/gt/3301620 logical tumors. [10][11][12][13] Here, we describe experimental studies with a recombinant herpes simplex virus (R7020) that is non-pathogenic in human studies and yet is highly destructive to specific tumors in mice.…”

Section: Ential Results In Antitumor Efficacy Between the Two Cell LImentioning

confidence: 99%

The use of a genetically engineered herpes simplex virus (R7020) with ionizing radiation for experimental hepatoma

Advani

et al. 2002

Gene Ther

View full text Add to dashboard Cite

The herpes simplex virus (HSV) recombinant virus R7020 is an attenuated virus designed as a candidate for immunization against both HSV-1 and HSV-2 infections. It was extensively tested in an experimental animal system and in a healthy human adult population without significant untoward effects. We report on the use of R7020 with ionizing radiation as an oncolytic agent for hepatomas. Two hepatoma cell lines were studied, Hep3B and Huh7. R7020 replicated to higher titers in Hep3B cells than in Huh7 cells. Tissue culture studies correlated with hepatoma xenograft responses to R7020. R7020 was more effective in mediating Hep3B tumor xenograft regression compared with Huh7. Ionizing radiation combined with R7020 also showed differential results in antitumor efficacy between the two cell lines in tumor xenografts. Ionizing radiation enhanced the replication of R7020 in Hep3B xenografts. Moreover, the combination of ionizing radiation and virus caused a greater regression of xenograft volume than either R7020 or radiation alone. Ionizing radiation had no effect on the replication of R7020 virus in Huh7 xenografts. These results indicate that a regimen involving infection with an appropriate herpesvirus such as R7020 in combination with ionizing radiation can be highly effective in eradicating certain tumor xenografts.

show abstract

Section: Ential Results In Antitumor Efficacy Between the Two Cell LImentioning

confidence: 99%

The use of a genetically engineered herpes simplex virus (R7020) with ionizing radiation for experimental hepatoma

Advani

et al. 2002

Gene Ther

View full text Add to dashboard Cite

show abstract

“…Six days after the R849 injection, histological change was examined by H-E staining (a) and X-gal staining to demonstrate the expression of the lacZ gene (b, c). Effect of HMBA on the antitumor activity of c 1 34.5-deficient HSV-1 S Naito et al Lee et al 13 reported that higher concentrations of HMBA were toxic to all the human pancreatic carcinoma cell lines they tested, and so performed experiments at a concentration of 0.5 mM. They found a modest increase in the production of G207 after 4 h of exposure to 0.5 mM HMBA for all pancreatic cancer cell lines; the increase was 1.5 to 35-fold.…”

Section: Discussionmentioning

confidence: 99%

“…4 Since the g 1 34.5 gene is responsible for the neurovirulence of HSV-1, 5,6 g 1 34.5 gene-deficient mutants are considered to be useful vectors for oncolytic therapy. So far, a number of malignant tumors including breast cancer, 7 prostate cancer, 8 lung cancer, 9 ovarian cancer, 10 malignant melanoma, 11 malignant glioma, 12 pancreatic cancer, 13 and head and neck cancer, 14,15 have been tested for sensitivity to oncolytic therapy using g 1 34.5 gene-deficient mutants. Despite encouraging preclinical studies, results from clinical trials suggest that current oncolytic viruses, although safe, exert only limited antitumor activity on their own.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of antitumor activity of herpes simplex virus γ134.5-deficient mutant for oral squamous cell carcinoma cells by hexamethylene bisacetamide

et al. 2006

View full text Add to dashboard Cite

Current oncolytic viruses exert only limited antitumor activity on their own. There is a need to increase their oncolytic capability. We evaluated the effect of a differentiating reagent, hexamethylene bisacetamide (HMBA), on the antitumor activity of a g 1 34.5-deficient herpes simplex virus type 1 (HSV-1) R849 for human oral squamous cell carcinoma (SCC) cells. Hexamethylene bisacetamide increased the viral yield, especially at a low input multiplicity of infection (MOI), and the transcription of immediate early genes of HSV-1. Hexamethylene bisacetamide treatment promoted the cytopathic effect of R849 and increased the proportion of dead cells. Hexamethylene bisacetamide produced more apoptotic cells in R849-infected cells as compared with parental HSV-1(F)-infected cells. The growth of oral SCC xenografts in nude mice was markedly suppressed by treatment with R849 in combination with HMBA, and the survival of the co-treated animals was significantly prolonged as compared with that of animals treated with R849 only. Herpes simplex virus type 1 mRNA was expressed in tumors and trigeminal neurons, but not in brain, lung, liver, and kidney. These results indicate that HMBA enhances the antitumor activity of R849 through the expression of immediate early genes without increasing its toxicity. Hexamethylene bisacetamide can be used as an enhancing agent for oncolytic therapy with HSV-1 mutants.

show abstract

“…HSV, a large double‐stranded DNA virus, has been extensively investigated as a platform for PDA‐directed therapy since the late 1990s. Preclinical data published by Lee et al in 1999 showed that G207, an HSV‐1 virus with deletions in both copies of ICP34.5 (to decrease neurovirulence) and genetic inactivation of ICP6 (to increase specificity for actively dividing cells) lysed PDA cells in vitro . G207 and NV1020—an OV with deletion in only one copy of γ 1 34.5 and intact ICP6—induced complete tumor eradication in 25% and 40%, respectively, when injected into mouse xenograft tumors .…”

Section: Oncolytic Virusesmentioning

confidence: 99%

Oncolytic viral therapy for pancreatic cancer

Rahal

Musher

2017

Journal of Surgical Oncology

View full text Add to dashboard Cite

Outcomes of pancreatic adenocarcinoma (PDA) remain dismal despite extensive clinical investigation. Combination chemotherapy provides modest improvements in survival above best supportive care, and immunotherapy has thus far not proven effective. Nevertheless, growing insight into antitumor immunity and the tumor microenvironment has inspired the discovery of novel agents targeting PDA. Oncolytic viruses represent an emerging class of immunotherapeutic agents that have undergone extensive preclinical investigation and warrant further investigation in well-designed clinical trials.

show abstract

G207, modified herpes simplex virus type 1, kills human pancreatic cancer cells in vitro

Cited by 21 publications

References 18 publications

The use of a genetically engineered herpes simplex virus (R7020) with ionizing radiation for experimental hepatoma

The use of a genetically engineered herpes simplex virus (R7020) with ionizing radiation for experimental hepatoma

Enhancement of antitumor activity of herpes simplex virus γ134.5-deficient mutant for oral squamous cell carcinoma cells by hexamethylene bisacetamide

Oncolytic viral therapy for pancreatic cancer

Contact Info

Product

Resources

About