A safety and immunogenicity study of immunization with hVEGF/RFASE in cynomolgus monkeys

Madelon Q Wentink, Henk M W Verheul, Arjan W Griffioen, Kenneth A Schafer, Susan McPherson, Richard J Early, Hans J van der Vliet, Tanja D de Gruijl

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INTRODUCTION: Vascular endothelial growth factor (VEGF) is pivotal in tumor angiogenesis and therapies targeting the VEGF axis are widely used in the clinic for the treatment of cancer. We have developed a therapeutic vaccine targeting human (h)VEGF165. hVEGF26-104/RFASE is based on the truncated protein hVEGF26-104 as antigen formulated in an oil-in-water emulsion containing the sulpholipopolysaccharide RFASE as adjuvant. Here we describe the toxicity and immunogenicity of this therapeutic vaccine in cynomolgus monkeys.

METHODS: In total 54 cynomolgus monkeys were used and divided in 7 groups. Groups 1-3 were control groups, either receiving PBS alone (group 1), RFASE alone (group 2) or hVEGF26-104 alone (group 3). Animals allocated to groups 4-7 received hVEGF26-104 together with RFASE, but with varying doses of the antigen or the adjuvant. All animals were immunized four times with 2-week intervals and safety and immunogenicity were monitored until 3 days after the final immunization.

RESULTS: Immunization induced an RFASE adjuvant dependent acute phase response. High titers of antibodies against hVEGF26-104 and cross-reactive with hVEGF165, were found in monkey sera, 28 days after primer immunization. These antibodies were able to inhibit the binding of the monoclonal antibody bevacizumab with hVEGF165 in a competition ELISA. Moreover, the biological activity of hVEGF165 could be inhibited by the addition of immunized monkey serum in a VEGF specific bioassay. Importantly, no adverse events commonly observed with VEGF neutralization were observed throughout the study.

CONCLUSION: These data show that hVEGF26-104/RFASE can be safely administered in cynomolgus monkeys, induces the desired immune response and therefore support the clinical development of this vaccine.

Original languageEnglish
Pages (from-to)2025-2032
Number of pages8
Issue number15
Publication statusPublished - 5 Apr 2018

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