A safety and immunogenicity study of immunization with hVEGF_26-104/RFASE in cynomolgus monkeys

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. 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.

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.

Immunization induced an RFASE adjuvant dependent acute phase response. High titers of antibodies against hVEGF_26-104 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.

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.