Potential mechanisms involved on how systemic IgG antibodies specific to vascular endothelial growth factor (VEGF) and induced by active immunotherapy decrease platelet derived free-VEGF.

CIGB-247 is a vascular endothelial growth factor (VEGF)-based active immunotherapy and it is currently under investigation for cancer treatment. This specific active immunotherapy encompasses two vaccine candidates that use a human VEGF variant molecule as antigen, in combination with two clinically tested adjuvants: VSSP or aluminum phosphate. CIGB-247 has been evaluated in patients with advanced solid tumors, recruited in two phase I clinical trials, and it has been shown to be safe and immunogenic by activating both cellular and humoral immune responses against human VEGF.

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program.

Background: CIGB-247 is a cancer therapeutic vaccine that uses as antigen a variant of human vascular endothelial growth factor (VEGF) mixed with the bacterially-derived adjuvant VSSP. CIGB-247 has been already evaluated in two 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.

Does VEGF-targeted active immunotherapy induce complete abrogation of platelet VEGF levels?

Objectives: Vascular endothelial growth factor (VEGF) is involved in physiological angiogenesis, but also is considered one of the key factors that promotes tumor angiogenesis. CIGB-247 is a VEGF-based vaccine that has been evaluated in phase I clinical trial patients with advanced solid tumors. This specific active immunotherapy is able to reduce platelet VEGF levels; however it is unknown whether this effect leads to a decrease in VEGF below the levels that can be observed in healthy individuals.

Evaluation of methodologies to determine the effect of specific active immunotherapy on VEGF levels in phase I clinical trial patients with advanced solid tumors.

Two phase I clinical trials were conducted to evaluate, among other parameters, the humoral response elicited by a vascular endothelial growth factor (VEGF)-based therapeutic vaccine in cancer patients with advanced solid tumors. VEGF reduction was studied using an indirect methodology named as "Platelet VEGF". This methodology is based on the estimation of VEGF within platelets by subtracting the plasma VEGF level from the serum level and dividing this by the platelet count, and then this latter expression is additionally corrected by the hematocrit.

Specific active immunotherapy with the HEBERSaVax VEGF-based cancer vaccine: From bench to bedside.

HEBERSaVax is a cancer therapeutic vaccine candidate based on the combination of a recombinant antigen representative of human vascular endothelial growth factor (VEGF), and clinically tested adjuvants. The vaccine has been shown to inhibit tumor growth and metastases in mice, and to induce VEGF-blocking antibodies and specific T-cell responses in several animal species, all with an excellent safety profile. After preclinical studies, two sequential phase 1 clinical trials were conducted with HEBERSaVax to assess safety, tolerance, and immunogenicity in patients with advanced solid tumors, at different antigen doses, and combined with two distinct adjuvants.

Characteristics of the specific humoral response in patients with advanced solid tumors after active immunotherapy with a VEGF vaccine, at different antigen doses and using two distinct adjuvants.

Background: CIGB-247, a VSSP-adjuvanted VEGF-based vaccine, was evaluated in a phase I clinical trial in patients with advanced solid tumors (CENTAURO). Vaccination with the maximum dose of antigen showed an excellent safety profile, exhibited the highest immunogenicity and was the only one showing a reduction on platelet VEGF bioavailability. However, this antigen dose level did not achieve a complete seroconversion rate in vaccinated patients.

Indirect and competitive enzyme-linked immunosorbent assays for monitoring the humoral response against human VEGF.

CIGB-247, a VEGF-based vaccine, was studied in a clinical trial. This advance demands the refinement of the methodologies for assessment of vaccine immune responses. This study aimed to improve the performance of ELISAs for detecting IgG antibodies against human VEGF and the blocking activity of the serum to inhibit the VEGF/VEGFR2 interaction.

Validation of a flow cytometry based binding assay for evaluation of monoclonal antibody recognizing EGF receptor.

An ideal test used to characterize a product must be appropriate for the measurement of product quality, manufacturing consistency, product stability, and comparability studies. Flow cytometry has been successfully applied to the examination of antibodies and receptors on membrane surfaces; however, to date, the analytical validation of cytometry based assays is limited. Here we report on the validation of a flow cytometry-based assay used in the evaluation of nimotuzumab binding to cells over-expressing EGFR on cell surface.