Immunogenicity and some safety features of a VEGF-based cancer therapeutic vaccine in rats, rabbits and non-human primates.
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.
Morera
Yanelys
Y
Recombinant Antibodies Laboratory, Dept. of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Cubanacán, Playa Havana 10600, Cuba. yanelys.morera@cigb.edu.cu
Bequet-Romero
Mónica
M
Ayala
Marta
M
Velazco
Jorge Castro
JC
Pérez
Pedro Puente
PP
Alba
Jesús Suárez
JS
Ancizar
Julio
J
Rodríguez
Meilyn
M
Cosme
Karelia
K
Gavilondo
Jorge V
JV
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000302:isolation & purification; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000302:isolation & purification; D019496:Cancer Vaccines / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D016663:Cercopithecinae; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D016233:Immunotherapy, Active / Q000379:methods*; D008081:Liposomes / Q000008:administration & dosage / Q000302:isolation & purification; D051379:Mice; D009345:Neisseria meningitidis / Q000737:chemistry; D009369:Neoplasms / Q000628:therapy*; D009829:Oleic Acids / Q000008:administration & dosage; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D001425:Bacterial Outer Membrane Proteins; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D008081:Liposomes; D009829:Oleic Acids; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A