Oncotarget

Research Papers: Immunology:

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

Sofie Denies, Laetitia Cicchelero, Ingeborgh Polis and Niek N. Sanders _

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Oncotarget. 2016; 7:10905-10916. https://doi.org/10.18632/oncotarget.7265

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Abstract

Sofie Denies1, Laetitia Cicchelero1, Ingeborgh Polis2 and Niek N. Sanders1

1 Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium

2 Small Animal Hospital, Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium

Correspondence to:

Niek N. Sanders, email:

Keywords: immunotherapy, DNA vaccine, electroporation, VEGFR-2, cancer, Immunology and Microbiology Section, Immune response, Immunity

Received: September 13, 2015 Accepted: January 18, 2016 Published: February 08, 2016

Abstract

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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