A safety and immunogenicity study of immunization with hVEGF26-104/RFASE in cynomolgus monkeys.

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)VEGF 165 . hVEGF 26-104 /RFASE is based on the truncated protein hVEGF 26-104 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 hVEGF 26-104 alone (group 3). Animals allocated to groups 4–7 received hVEGF 26-104 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 hVEGF 26-104 and cross-reactive with hVEGF 165 , were found in monkey sera, 28 days after primer immunization. These antibodies were able to inhibit the binding of the monoclonal antibody bevacizumab with hVEGF 165 in a competition ELISA. Moreover, the biological activity of hVEGF 165 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 hVEGF 26-104 /RFASE can be safely administered in cynomolgus monkeys, induces the desired immune response and therefore support the clinical development of this vaccine. [ABSTRACT FROM AUTHOR]