Immunogenicity and some safety features of a VEGF-based cancer therapeutic vaccine in rats, rabbits and non-human primates

• Published in: Vaccine Vol. 28; no. 19; pp. 3453 - 3461
• Main Authors: Morera, Yanelys, Bequet-Romero, Mónica, Ayala, Marta, Velazco, Jorge Castro, Pérez, Pedro Puente, Alba, Jesús Suárez, Ancizar, Julio, Rodríguez, Meilyn, Cosme, Karelia, Gavilondo, Jorge V
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 26.04.2010; Elsevier; Elsevier Limited
• Subjects: Adjuvants; Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - isolation & purification; Allergy and Immunology; Angiogenesis; Animals; Antibodies, Neoplasm - blood; Applied microbiology; Bacterial Outer Membrane Proteins - administration & dosage; Bacterial Outer Membrane Proteins - isolation & purification; Biological and medical sciences; Breeding of animals; Cancer; Cancer Vaccines - adverse effects; Cancer Vaccines - genetics; Cancer Vaccines - immunology; Cercopithecinae; Chromatography; Cloning; E coli; Female; Fundamental and applied biological sciences. Psychology; Genetic engineering; Humans; Immunization, Secondary; Immunoglobulin G - blood; Immunotherapy, Active - methods; Injections; Laboratory animals; Liposomes - administration & dosage; Liposomes - isolation & purification; Medical sciences; Mice; Microbiology; Monkeys & apes; Neisseria meningitidis; Neisseria meningitidis - chemistry; Neoplasms - therapy; Oleic Acids - administration & dosage; Proteins; Rabbits; Rats; Rats, Wistar; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Rodents; T-Lymphocytes - immunology; Tumors; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - immunology; VEGF; Wound healing; VEGF; Vaccine; Cancer; Rat; Rodentia; Monkey; Rabbit; Malignant tumor; Lagomorpha; Vertebrata; Mammalia; Immunogenicity; Immunotherapy; Primates
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.02.069

Abstract We have developed a cancer vaccine candidate (hereafter denominated CIGB-247), based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, and the adjuvant VSSP (very small sized proteoliposomes of Neisseria meningitidis outer membrane). In mice, previous work of our group had shown that vaccination with CIGB-247 extended tumor-take time, slowed tumor growth, and increased animal survival. Immunization elicited anti-human and murine VEGF-neutralizing antibodies, and spleen cells of vaccinated mice are cytotoxic in vitro to tumor cells that produce VEGF. We have now tested the immunogenicity of CIGB-247 in Wistar rats, New Zealand White rabbits and the non-human primate Chlorocebus aethiops sabaeus . Using weekly, biweekly and biweekly plus montanide immunization schemes, all three species develop antigen-specific IgG antibodies that can block the interaction of VEGF and VEGF receptor 2 in an ELISA assay. Antibody titers decline after vaccination stops, but can be boosted with new immunizations. In monkeys, DTH and direct cell cytotoxicity experiments suggest that specific T-cell responses are elicited by vaccination. Immunization with CIGB-247 had no effect on normal behavior, hematology, blood biochemistry and histology of critical organs, in the tested animals. Skin deep wound healing was not affected in vaccinated rats and monkeys.