Effect of a Novel DNA Vaccine on Angiogenesis and Tumor Growth In Vivo

McKinney, Kibwei A.; Al-Rawi, Nada; Maciag, Paulo; Banyard, Derek A.; Sewell, David L.

doi:10.1001/archoto.2010.139

Cited by 8 publications

(5 citation statements)

References 19 publications

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“…The DNA thus elicits both the arms of immune response following in vivo expression of the antigen [1]. It has been endeavoured for the treatment of autoimmunity [2], cancer [3], allergic diseases [4] bacterial infections [5] and viral diseases [6]. Several strategies have been proposed to improve the efficacy of DNA vaccine, such as the use of liposomes [7], inclusion of CpG motif [8], administration of plasmid expressing costimulatory molecules and cytokines [9], exploring different routes of administration of vaccine [10-12] and targeting the vaccine to specific cells [13].…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of macrophage associated vectors for use in genetic vaccine

Ahsan

Gore

2011

Genet Vaccines Ther

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BackgroundAntigen presentation by non professional antigen presenting cells (APC) can lead to anergy. In genetic vaccines, targeting the macrophages and APC for efficient antigen presentation might lead to balanced immune response. One such approach is to incorporate APC specific promoter in the vector to be used.MethodsThree promoters known to be active in macrophage were selected and cloned in mammalian expressing vector (pAcGFP1-N1) to reconstruct (pAcGFP-MS), (pAcGFP-EMR) and (pAcGFP-B5I) with macrosialin, EmrI and Beta-5 Integrin promoters respectively. As a positive control (pAcGFP-CMV) was used with CMV promoter and promoterless vector (pAcGFP-NIX) which served as a negative control. GFP gene was used as readout under the control of each of the promoter. The expression of GFP was analyzed on macrophage and non-macrophage cell lines using Flow cytometry and qRT-PCR with TaqMan probe chemistries.ResultsAll the promoters in question were dominant to macrophage lineage cell lines as observed by fluorescence, Western blot and quantitative RT-PCR. The activity of macrosialin was significantly higher than other macrophage promoters. CMV promoter showed 1.83 times higher activity in macrophage cell lines. The expression of GFP driven by macrosialin promoter after 24 hours was 4.40 times higher in macrophage derived cell lines in comparison with non macrophage cell lines.ConclusionsBased on this study, macrosialin promoter can be utilized for targeting macrophage dominant expression. In vivo study needs to be carried out for its utility as a vaccine candidate.

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Section: Introductionmentioning

confidence: 99%

Comparative analysis of macrophage associated vectors for use in genetic vaccine

Ahsan

Gore

2011

Genet Vaccines Ther

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“…Biological vectors also raise safety concerns [ 34 ]. Vaccination with naked plasmid is evaluated in three research papers [ 35 - 37 ]. Transfection efficiency of naked plasmid however is very low, making this approach far from optimal.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and safety of xenogeneic vascular endothelial growth factor receptor-2 DNA vaccination in mice and dogs

et al. 2016

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Vascular endothelial growth factor receptor-2 (VEGFR-2) is an attractive target in oncology due to its crucial role in angiogenesis. In this study a DNA vaccine coding for human VEGFR-2 was evaluated in healthy mice and dogs, administered by intradermal injection and electroporation. In mice, three doses and vaccination schedules were evaluated. Cellular immune responses were measured by intracellular IFN-gamma staining and a cytotoxicity assay and antibodies by ELISA. Safety was assessed by measuring regulatory T cells and myeloid derived suppressor cells and a wound healing assay. The vaccine was subsequently evaluated in dogs, which were vaccinated three times with 100μg. Cellular immune responses were measured by intracellular IFN-gamma staining and antibodies by a flow cytometric assay. In mice, maximal cellular responses were observed after two vaccinations with 5μg. Humoral responses continued to increase with higher dose and number of vaccinations. No abnormalities in the measured safety parameters were observed. The vaccine was also capable of eliciting a cellular and humoral immune response in dogs. No adverse effects were observed, but tolerability of the electroporation was poor. This study will facilitate the evaluation of the vaccine in tumor bearing animals, ranging from rodent models to dogs with spontaneous tumors.

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“…The substrate-binding site can be applied to shear the RNA of a variety of pathogens and mRNAs of disease-related genes after changing its sequence composition in the 10–23 DNA enzyme [31, 32]. In gene therapy, 10–23 DNA enzymes have the advantages of both the ribozyme (Rz) and antisense oligodeoxynucleotide (ASODN) [33, 34].…”

Section: Discussionmentioning

confidence: 99%

Transfected Early Growth Response Gene-1 DNA Enzyme Prevents Stenosis and Occlusion of Autogenous Vein GraftIn Vivo

Wang

Cheng

et al. 2013

BioMed Research International

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The aim of this study was to detect the inhibitory action of the early growth response gene-1 DNA enzyme (EDRz) as a carrying agent by liposomes on vascular smooth muscle cell proliferation and intimal hyperplasia. An autogenous vein graft model was established. EDRz was transfected to the graft vein. The vein graft samples were obtained on each time point after surgery. The expression of the EDRz transfected in the vein graft was detected using a fluorescent microscope. Early growth response gene-1 (Egr-1) mRNA was measured using reverse transcription-PCR and in situ hybridization. And the protein expression of Egr-1 was detected by using western blot and immunohistochemistry analyses. EDRz was located at the media of the vein graft from 2 to 24 h, 7 h after grafting. The Egr-1 protein was mainly located in the medial VSMCs, monocytes, and endothelium cells during the early phase of the vein graft. The degree of VSMC proliferation and thickness of intima were obviously relieved compared with the no-gene therapy group. EDRz can reduce Egr-1 expression in autogenous vein grafts, effectively restrain VSMC proliferation and intimal hyperplasia, and prevent vascular stenosis and occlusion after vein graft.

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Effect of a Novel DNA Vaccine on Angiogenesis and Tumor Growth In Vivo

Abstract: The novel DNA cancer vaccine LLO-Flk1 can slow tumor growth in vivo.

Cited by 8 publications

References 19 publications

Comparative analysis of macrophage associated vectors for use in genetic vaccine

Comparative analysis of macrophage associated vectors for use in genetic vaccine

Immunogenicity and safety of xenogeneic vascular endothelial growth factor receptor-2 DNA vaccination in mice and dogs

Transfected Early Growth Response Gene-1 DNA Enzyme Prevents Stenosis and Occlusion of Autogenous Vein GraftIn Vivo

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