Specific humoral response in cancer patients treated with a VEGF therapeutic vaccine under a compassionate use program

Abstract

Background: CIGB-247 is a cancer therapeutic vaccine that uses as antigen a variant of human vascular endothelial growth factor (VEGF) mixed with the bacterial-derived adjuvant VSSP. This VEGF vaccine has been evaluated in phase I clinical trials CENTAURO and CENTAURO-2, showing to be safe and immunogenic in advanced cancer patients selected under well-defined and controlled clinical conditions. Surviving patients were submitted to monthly re-immunizations and some of them showed objective clinical benefits. These observations led us to initiate a compassionate use program of CIGB-247 in patients who do not meet entry criteria applied for CENTAURO and CENTAURO-2 clinical trials. Results: This report shows the characterization of the humoral response elicited after vaccination with 400 µg of antigen combined with 200 µg of VSSP in cancer patients representative of the Cuban real clinical practice setting. Polyclonal antibody response was specific to VEGF, and showed no cross reactivity with other VEGF family members like VEGF-C and VEGF-D. Specific IgM, IgA and IgG antibodies detected in the serum of vaccinated patients were able to block the binding of VEGF to its receptors VEGFR1 and VEGFR2. Serum-purified IgG fraction exhibited all these properties. For the first time, there is experimental evidence of the presence of polyclonal antibodies directed to clinically relevant epitopes on VEGF. These elicited antibodies impaired the high affinity interaction between VEGF and monoclonal antibody Bevacizumab, an antiangiogenic drug approved in combination with chemotherapy for the treatment of different tumors. This investigation also shows preliminary evidences of safety and immunogenicity of CIGB-247 in cancer patients under clinical conditions not yet explored. Conclusions: CIGB-247 was immunogenic in a broader patient population, and induced Bevacizumab-like polyclonal antibodies, indicating that the VEGF-specific antibody response could have a potentially relevant clinical activity.