Inhibition of angiogenesis by a Semliki Forest virus vector expressing VEGFR-2 reduces tumour growth and metastasis in mice

Lyons, Janice A.; Sheahan, B. J.; Galbraith, Sareen E.; Mehra, Reena; Atkins, Gregory J.; Fleeton, Marina N.

doi:10.1038/sj.gt.3302889

Cited by 40 publications

(30 citation statements)

References 38 publications

(74 reference statements)

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“…Such viral-vector vaccines attempt to employ the natural immunogenicity of a viral infection to target responses against tumor-specific antigens artificially incorporated into the viral genome, but have shown limited clinical success [155]. A recent study using a Semliki Forest virus-like particle encoding VEGFR-2 was recently reported to induce antiangiogenic and antitumor effects in mouse tumor models treated both prophylactically and therapeutically [156]. Investigators have studied numerous live viruses for vaccine purposes, including pox-, adeno-and herpes S viruses.…”

Section: Five-year Viewmentioning

confidence: 98%

Immunotherapy against angiogenesis-associated targets: evidence and implications for the treatment of malignant glioma

Everson

Graner

Gromeier

et al. 2008

Expert Review of Anticancer Therapy

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Angiogenesis, the growth of new blood vessels from previously existing vasculature, is a requirement for tumor growth and metastasis. The first US FDA-approved drugs targeting angiogenesis have shown potential in the treatment of malignant gliomas. Immunotherapy as a treatment modality lends itself well to specifically targeting angiogenesis in tumors and may represent a powerful tool in the treatment of malignant gliomas. This review focuses on developments in immunotherapy targeting angiogenesis and tumor-vascular-specific endothelial cells using a variety of immunotherapeutic strategies including monoclonal antibodies and conjugated immunotoxins, as well as cellular, peptide, DNA and dendritic cell vaccines.

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Section: Five-year Viewmentioning

confidence: 98%

Immunotherapy against angiogenesis-associated targets: evidence and implications for the treatment of malignant glioma

Everson

Graner

Gromeier

et al. 2008

Expert Review of Anticancer Therapy

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“…Administration of replication-deficient vectors encoding reporter or immunomodulator genes, such as cytokines or growth factors, has also been demonstrated. This leads to successful tumor inhibition or complete regression in animal models [16-19]. Nevertheless, the application of alphaviral immunogene therapy in a clinical study using Venezuelan equine encephalitis (VEE) virus (VEE/CEA) in phase I/II demonstrated insufficient anti-tumor efficacy in patients, most likely due to the inefficient induction of anti-tumor immune responses in patients with end-stage disease [20].…”

Section: Introductionmentioning

confidence: 99%

High efficiency of alphaviral gene transfer in combination with 5-fluorouracil in a mouse mammary tumor model

et al. 2014

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BackgroundThe combination of virotherapy and chemotherapy may enable efficient tumor regression that would be unachievable using either therapy alone. In this study, we investigated the efficiency of transgene delivery and the cytotoxic effects of alphaviral vector in combination with 5-fluorouracil (5-FU) in a mouse mammary tumor model (4 T1).MethodsReplication-deficient Semliki Forest virus (SFV) vectors carrying genes encoding fluorescent proteins were used to infect 4 T1 cell cultures treated with different doses of 5-FU. The efficiency of infection was monitored via fluorescence microscopy and quantified by fluorometry. The cytotoxicity of the combined treatment with 5-FU and alphaviral vector was measured using an MTT-based cell viability assay. In vivo experiments were performed in a subcutaneous 4 T1 mouse mammary tumor model with different 5-FU doses and an SFV vector encoding firefly luciferase.ResultsInfection of 4 T1 cells with SFV prior to 5-FU treatment did not produce a synergistic anti-proliferative effect. An alternative treatment strategy, in which 5-FU was used prior to virus infection, strongly inhibited SFV expression. Nevertheless, in vivo experiments showed a significant enhancement in SFV-driven transgene (luciferase) expression upon intratumoral and intraperitoneal vector administration in 4 T1 tumor-bearing mice pretreated with 5-FU: here, we observed a positive correlation between 5-FU dose and the level of luciferase expression.ConclusionsAlthough 5-FU inhibited SFV-mediated transgene expression in 4 T1 cells in vitro, application of the drug in a mouse model revealed a significant enhancement of intratumoral transgene synthesis compared with 5-FU untreated mice. These results may have implications for efficient transgene delivery and the development of potent cancer treatment strategies using alphaviral vectors and 5-FU.

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“…CT26 colon carcinoma was chosen because of its sensitivity to PTX [18] and angiogenic properties [19]. CT26 colon carcinoma cells were inoculated subcutaneously in the right flank (for antitumor efficacy and biodistribution studies) or in the right leg (for MRI studies) of BALB/c mice (5 Â 10 4 cells per mouse) depending on the experiment (see Note 3) [20].…”

Section: Animal Tumor Modelmentioning

confidence: 99%

Tumor Targeting by RGD-Grafted PLGA-Based Nanotheranostics Loaded with Paclitaxel and Superparamagnetic Iron Oxides

Danhier

Schleich

et al. 2015

Methods in Pharmacology and Toxicology

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Theranostic nanoparticles have the potential to revolutionize cancer diagnosis and therapy. Many groups have demonstrated differential levels of tumor growth between tumors treated by targeted or untargeted nanoparticles; however, only few have shown in vivo efficacy in both therapeutic and diagnostic approach. Herein, we first develop and characterize dual-paclitaxel (PTX)/superparamagnetic iron oxide (SPIO)-loaded PLGA-based nanoparticles grafted with the RGD peptide, for a theranostic purpose. Second, we compare in vivo different strategies in terms of targeting capabilities: (1) passive targeting via the EPR effect, (2) active targeting of α v β 3 integrin via RGD grafting, (3) magnetic guidance via a magnet placed on the tumor, and (4) the combination of the magnetic guidance and the active targeting of α v β 3 integrin. In this chapter, we present the general flowchart applied for this project: (1) the polymer and SPIO synthesis, (2) the physicochemical characterization of the nanoparticles, (3) the magnetic properties of the nanoparticles, and (4) the in vivo evaluation of the nanoparticles for their therapeutic and diagnosis purposes. We employ the electron spin resonance spectroscopy and magnetic resonance imaging to both quantify and visualize the accumulation of theranostic nanoparticles into the tumors.

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Inhibition of angiogenesis by a Semliki Forest virus vector expressing VEGFR-2 reduces tumour growth and metastasis in mice

Cited by 40 publications

References 38 publications

Immunotherapy against angiogenesis-associated targets: evidence and implications for the treatment of malignant glioma

Immunotherapy against angiogenesis-associated targets: evidence and implications for the treatment of malignant glioma

High efficiency of alphaviral gene transfer in combination with 5-fluorouracil in a mouse mammary tumor model

Tumor Targeting by RGD-Grafted PLGA-Based Nanotheranostics Loaded with Paclitaxel and Superparamagnetic Iron Oxides

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