Experimental studies of a vaccine formulation of recombinant human VEGF antigen with aluminum phosphate

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 re...

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Bibliographic Details
Published in:	Human vaccines & immunotherapeutics Vol. 11; no. 8; pp. 2030 - 2037
Main Authors:	Pérez Sánchez, Lincidio, Morera Díaz, Yanelys, Bequet-Romero, Mónica, Ramses Hernández, Gerardo, Rodríguez, Yadira, Castro Velazco, Jorge, Puente Pérez, Pedro, Ayala Avila, Marta, Gavilondo, Jorge V
Format:	Journal Article
Language:	English
Published:	United States Taylor & Francis 03-08-2015
Subjects:	adjuvant Adjuvants, Immunologic - administration & dosage Aluminum Compounds - administration & dosage Aluminum phosphate Animals antibodies Antibodies, Neutralizing - blood cancer therapeutic vaccine Cancer Vaccines - administration & dosage Cancer Vaccines - genetics Cancer Vaccines - immunology Cercopithecus aethiops Chemistry, Pharmaceutical Cytotoxicity, Immunologic Female Immunization Schedule Leukocytes, Mononuclear - immunology Male Mammary Neoplasms, Animal - therapy Mammary Neoplasms, Experimental - therapy Mice, Inbred BALB C Mice, Inbred C57BL Neoplasm Metastasis - prevention & control Phosphates - administration & dosage Research Papers Vaccines, Synthetic - administration & dosage Vaccines, Synthetic - genetics Vaccines, Synthetic - immunology Vascular Endothelial Growth Factor A - immunology VEGF CFSE, Carboxyfluorescein succinimidyl ester FACS, Fluorescence-activated cell sorting VEGF KDR, kinase domain receptor VEGF, vascular endothelial growth factor ELISA, Enzyme-linked immune-sorbent assay HPLC, High-performance liquid chromatography cancer therapeutic vaccine PBMC, Peripheral blood mononuclear cells Ni-NTA, nickel-nitrilotriacetic acid VSSP, very small sized proteoliposomes adjuvant ANOVA, Analysis of Variance Aluminum phosphate antibodies GST, Glutathione S-transferase CTL, Cytotoxic T lymphocyte VEGFR2, vascular endothelial growth factor receptor 2
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2164-5515 2164-554X
DOI:	10.1080/21645515.2015.1029213