CIGB-247 is a cancer vaccine that is a formulation of a recombinant protein antigen representative of the human vascular endothelial growth factor (VEGF) with a bacterially-derived adjuvant (VSSP). The vaccine has shown an excellent safety profile in mice, rats, rabbits, not-human primates and in recent clinical trials in cancer patients. Response to the vaccine is characterized by specific antibody titers that neutralize VEGF/VEGFR2 binding and a cytotoxic tumor-specific response. To expand our present anti-VEGF active immunotherapy strategies, we have now studied in mice and non-human primates the effects of vaccination with a formulation of our recombinant VEGF antigen and aluminum phosphate adjuvant (hereafter denominated CIGB-247-A). Administered bi-weekly, CIGB-247-A produces high titers of anti-VEGF IgG blocking antibodies in 2 mice strains. Particularly in BALB/c, the treatment impaired subcutaneous F3II mammary tumor growth and reduced the number of spontaneous lung macro metastases, increasing animals' survival. Spleen cells from specifically immunized mice directly killed F3II tumor cells in vitro. CIGB-247-A also showed to be immunogenic in non-human primates, which developed anti-VEGF blocking antibodies and the ability for specific direct cell cytotoxic responses, all without impairing the healing of deep skin wounds or other side effect. Our results support consideration of aluminum phosphate as a suitable adjuvant for the development of new vaccine formulations using VEGF as antigen.
Keywords: ANOVA, Analysis of Variance; Aluminum phosphate; CFSE, Carboxyfluorescein succinimidyl ester; CTL, Cytotoxic T lymphocyte; ELISA, Enzyme-linked immune-sorbent assay; FACS, Fluorescence-activated cell sorting; GST, Glutathione S-transferase; HPLC, High-performance liquid chromatography; KDR, kinase domain receptor; Ni-NTA, nickel-nitrilotriacetic acid; PBMC, Peripheral blood mononuclear cells; VEGF; VEGF, vascular endothelial growth factor; VEGFR2, vascular endothelial growth factor receptor 2; VSSP, very small sized proteoliposomes; adjuvant; antibodies; cancer therapeutic vaccine.