title: Experimental studies of a vaccine formulation of recombinant human VEGF antigen with aluminum phosphate.
abstract: 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.
authors.affiliation: a Cancer Immunotherapy Laboratory; Department of Pharmaceuticals; Center for Genetic Engineering and Biotechnology (CIGB) ; Playa Cubanacan , Havana , Cuba.
authors.forename: Lincidio
authors.initials: L
authors.lastname: Pérez Sánchez
authors.forename: Yanelys
authors.initials: Y
authors.lastname: Morera Díaz
authors.forename: Mónica
authors.initials: M
authors.lastname: Bequet-Romero
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ramses Hernández
authors.forename: Yadira
authors.initials: Y
authors.lastname: Rodríguez
authors.forename: Jorge
authors.initials: J
authors.lastname: Castro Velazco
authors.forename: Pedro
authors.initials: P
authors.lastname: Puente Pérez
authors.forename: Marta
authors.initials: M
authors.lastname: Ayala Avila
authors.forename: Jorge V
authors.initials: JV
authors.lastname: Gavilondo
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D017607:Aluminum Compounds / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002626:Chemistry, Pharmaceutical; D002522:Chlorocebus aethiops; D003602:Cytotoxicity, Immunologic; D005260:Female; D007115:Immunization Schedule; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000628:therapy; D008325:Mammary Neoplasms, Experimental / Q000628:therapy; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control; D010710:Phosphates / Q000008:administration & dosage*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D057134:Antibodies, Neutralizing; D019496:Cancer Vaccines; D010710:Phosphates; D014614:Vaccines, Synthetic; D042461:Vascular Endothelial Growth Factor A; C012714:aluminum phosphate
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