Lister strain of vaccinia virus armed with endostatin–angiostatin fusion gene as a novel therapeutic agent for human pancreatic cancer

Tysome, James R.; Briat, Arnaud; Alusi, Ghassan; Cao, Fang; Gao, Dongling; Yu, Jinxia; Wang, Pengju; Yang, Shaolong; Dong, Ziming; Wang, Shengdian; Deng, Lu; Francis, Jennelle; Timiryasova, Tatyana M.; Fodor, István; Lemoine, Nick R.; Wang, Yaohe

doi:10.1038/gt.2009.74

Cited by 57 publications

(61 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3 It was shown that the oncolytic adenovirus expressing a human endostatin and angiostatin fusion protein (hEA) imposed potent antiangiogenic effects and suppressed the prostate tumor growth in mouse models, 4 while the vaccinia virus expressing hEA also delayed the pancreatic cancer progression. 5 However, these vectors possess respective drawbacks. 3,6 For instance, adenovirus mounts potent immune responses while the packaging capacity of AAV is limited.…”

Section: Introductionmentioning

confidence: 99%

Development of the hybrid Sleeping Beauty-baculovirus vector for sustained gene expression and cancer therapy

et al. 2011

Gene Ther

View full text Add to dashboard Cite

Antiangiogenesis is an appealing anticancer approach but requires continued presence of the antiangiogenic agents, which can be remedied by gene therapy. Baculovirus is an emerging gene delivery vector but only mediates transient expression (o7 days); thus, this study primarily aimed to develop a hybrid baculovirus for sustained antiangiogenic gene expression and cancer therapy. We first constructed plasmids featuring adeno-associated virus inverted terminal repeats (AAV ITRs), oriP/ Epstein-Barr virus-expressed nuclear antigen 1 (EBNA1) or Sleeping Beauty (SB) transposon and compared their efficacies in terms of persistent expression. In human embryonic kidney (HEK293) cells, AAV ITR failed to prolong the expression while oriP/EBNA1 moderately extended the expression to 35 days. In contrast, the SB system led to stable expression beyond 77 days even without antibiotic selection. Given this finding, we constructed a hybrid SB baculovirus expressing the SB transposase and harboring the transgene cassette flanked by inverted repeat/direct-repeat (IR/DR) elements recognizable by SB. The hybrid SB baculovirus efficiently transduced mammalian cells and mediated an expression duration longer than that by conventional baculoviruses, thanks to the transgene persistence and integration. The SB baculovirus (Bac-SB-T2hEA/w) expressing the antiangiogenic fusion protein comprising endostatin and angiostatin (hEA) also enabled prolonged hEA expression. With sustained hEA expression, Bac-SB-T2hEA/w repressed the angiogenesis in vivo, hindered the growth of two different tumors (prostate tumor allografts and human ovarian tumor xenografts) in mice and extended the life span of animals. These data altogether implicated the potential of the hybrid SB-baculovirus vector for prolonged hEA expression and for the treatment of multiple types of angiogenesis-dependent tumors.

show abstract

Section: Introductionmentioning

confidence: 99%

Development of the hybrid Sleeping Beauty-baculovirus vector for sustained gene expression and cancer therapy

et al. 2011

Gene Ther

View full text Add to dashboard Cite

show abstract

“…These trials have indicated the inherent safety of the virus, efficacy of intravenous delivery of VV, VV infection of metastatic deposits, and reproducible disease control in many patients enrolled in the trials. However, along with other groups (9), we have observed that there is variability in cell killing by VV in different cancer cell lines, and the reasons for this are not fully understood (10).…”

mentioning

confidence: 68%

“…The statistical analysis was conducted using one-way ANOVA. *, P Ͻ 0.05; **, P Ͻ 0.01; ***, P Ͻ 0.001. ing vaccine strains, have been shown to inherently target tumors (10,35). This tumor selectivity is partially attributed to the activation of the epidermal growth factor/Ras-MEK-extracellular signal-regulated kinase (ERK) pathways and deregulation of interferon (IFN) pathways in cancer cells (36,37).…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor A Promotes Vaccinia Virus Entry into Host Cells via Activation of the Akt Pathway

Hiley

Chard

Gangeswaran

et al. 2013

J Virol

View full text Add to dashboard Cite

Vaccinia virus (VV) is an enveloped DNA virus from the poxvirus family and has played a crucial role in the eradication of smallpox. It continues to be used in immunotherapy for the prevention of infectious diseases and treatment of cancer. However, the mechanisms of poxvirus entry, the host factors that affect viral virulence, and the reasons for its natural tropism for tumor cells are incompletely understood. By studying the effect of hypoxia on VV infection, we found that vascular endothelial growth factor A (VEGF-A) augments oncolytic VV cytotoxicity. VEGF derived from tumor cells acts to increase VV internalization, resulting in increased replication and cytotoxicity in an AKT-dependent manner in both tumor cells and normal respiratory epithelial cells. Overexpression of VEGF also enhances VV infection within tumor tissue in vivo after systemic delivery. These results highlight the importance of VEGF expression in VV infection and have potential implications for the design of new strategies to prevent poxvirus infection and the development of future generations of oncolytic VV in combination with conventional or biological therapies.

show abstract

“…However, limited progress has been achieved in this field. To improve and replace combinational therapy, modifying anti-angiogenesis gene by genetic engineering to create novel fusion gene with higher activity, more powerful function and stability is receiving more and more attentions (19,20). ENDO-VEGI 151 is a novel anti-angiogenesis gene from our laboratory (4,5,21,22).…”

Section: Discussionmentioning

confidence: 99%

Anti-angiogenesis and anticancer effects of a plasmid expressing both ENDO-VEGI151 and small interfering RNA against survivin

Yang²,

Chang³

et al. 2011

Int J Mol Med

View full text Add to dashboard Cite

Abstract. We have previously reported that the overexpression of the endostatin-vascular endothelial cell growth inhibitor (VEGI) fusion protein inhibits angiogenesis and achieves a strong anticancer effect. In this study, we constructed the dualfunction expression plasmid pCDNA3.1-ENDO-VEGI 151 / survivin-small interfering RNA (siRNA) (pEV/si-survivin), and evaluated the anti-angiogenesis and anticancer effects of this plasmid. Efficient siRNA sequences against survivin were identified; and the pEV/si-survivin expression vector was constructed and transfected into MDA-MB-231 cells and human umbilical vein endothelial cells (HUVECs). The expression levels of ENDO-VEGI 151 and survivin were detected by RT-PCR and Western blotting analysis. MTT assay was used to detect the proliferation of cancer cell lines. Flow cytometry was used to detect cell cycle states and apoptosis. The expression of both ENDO-VEGI 151 and survivin-siRNA were detected in MDA-MB-231 and HUEVC cells transfected with pEV/si-survivin. The expression of survivin was reduced in cells transfected with pEV/si-survivin. Furthermore, pEV/ si-survivin inhibited proliferation and promoted apoptosis in MDA-MB-231 and HUEVC cells. It also caused cell cycle arrest in both cell lines. In conclusion, the dual-function expression plasmid pEV/si-survivin is involved in inhibition of angiogenesis and promoting tumor cell apoptosis in vitro. Therefore, it is also expected to improve the treatment of tumors by exerting synergistic effects in vivo. IntroductionMalignant tumor is one of the major diseases threatening human health and leads to high mortality. However, traditional therapeutic drugs targeting tumor angiogenesis have limited effect on the treatment of malignant tumors. Combination of tumor angiogenesis inhibitor (TAI) with other traditional anticancer methods causes unexpected toxicity and side-effect. Therefore, the exploration of novel combinational strategies has received wide attentions.Endostatin, a C-terminal fragment of type XVIII collagen, has been reported to be an efficient anti-angiogenesis agent. It reduces angiogenesis from both inhibiting the proliferation and migration and stimulating apoptosis of endothelial cells specifically (1). Previous studies revealed that endostatin treatment could inhibit tumor growth significantly (2). Vascular endothelial cell growth inhibitor (VEGI), a member of tumor necrosis factor (TNF) superfamily, has been shown to inhibit cancer through three different ways: directly sacrificing tumor cells; indirectly inhibiting the proliferation of endothelial cells; and stimulating the maturation of dendritic cells (3). Our previous studies showed the overexpression of endostatin-VEGI fusion protein inhibited angiogenesis and achieved strong anti-cancer effect (4,5).Survivin has been considered as the most effective inhibitor of cell apoptosis so far and widely expressed in human tumors. It is regarded as an ideal target for tumor gene therapy (6). In this study, we constructed the dual function expressional plasmi...

show abstract

Lister strain of vaccinia virus armed with endostatin–angiostatin fusion gene as a novel therapeutic agent for human pancreatic cancer

Cited by 57 publications

References 48 publications

Development of the hybrid Sleeping Beauty-baculovirus vector for sustained gene expression and cancer therapy

Development of the hybrid Sleeping Beauty-baculovirus vector for sustained gene expression and cancer therapy

Vascular Endothelial Growth Factor A Promotes Vaccinia Virus Entry into Host Cells via Activation of the Akt Pathway

Anti-angiogenesis and anticancer effects of a plasmid expressing both ENDO-VEGI151 and small interfering RNA against survivin

Contact Info

Product

Resources

About