title: Antigen dose escalation study of a VEGF-based therapeutic cancer vaccine in non human primates.
abstract: CIGB-247 is a cancer therapeutic, based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, in combination with the oil free adjuvant VSSP (very small sized proteoliposomes of Neisseria meningitidis outer membrane). Our previous experimental studies in mice with CIGB-247 have shown that the vaccine has both anti-tumoral and anti-metastatic activity, and produces both antibodies that block VEGF-VEGF receptor interaction, and a specific T-cell cytotoxic response against tumor cells. CIGB-247, with an antigen dose of 100 μg, has been characterized by an excellent safety profile in mice, rats, rabbits, and non human primates. In this article we extend the immunogenicity and safety studies of CIGB-247 in non human primates, scaling the antigen dose from 100 μg to 200 and 400 μg/vaccination. Our results indicate that such dose escalation did not affect animal behavior, clinical status, and blood parameters and biochemistry. Also, vaccination did not interfere with skin deep skin wound healing. Anti-VEGF IgG antibodies and specific T-cell mediated responses were documented at all three studied doses. Antigen dose apparently did not determine differences in maximum antibody titer during the 8 weekly immunization induction phase, or the subsequent increase in antibodies seen for monthly boosters delivered afterwards. Higher antigen doses had a positive influence in antibody titer maintenance, after cessation of immunizations. Boosters were important to achieve maximum antibody VEGF blocking activity, and specific T-cell responses in all individuals. Purified IgG from CIGB-247 immunized monkey sera was able to impair proliferation and formation of capillary-like structures in Matrigel, for HMEC cells in culture. Altogether, these results support the further clinical development of the CIGB-247 therapeutic cancer vaccine, and inform on the potential mechanisms involved in its effect.
authors.affiliation: Cancer Immunotherapy Laboratory, Department of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Playa Cubanacábn, Havana 10600, Cuba. yanelys.morera@cigb.edu.cu
authors.forename: Yanelys
authors.initials: Y
authors.lastname: Morera
authors.forename: Mónica
authors.initials: M
authors.lastname: Bequet-Romero
authors.forename: Marta
authors.initials: M
authors.lastname: Ayala
authors.forename: Pedro Puente
authors.initials: PP
authors.lastname: Pérez
authors.forename: Jorge
authors.initials: J
authors.lastname: Castro
authors.forename: Javier
authors.initials: J
authors.lastname: Sánchez
authors.forename: José Suárez
authors.initials: JS
authors.lastname: Alba
authors.forename: Julio
authors.initials: J
authors.lastname: Ancízar
authors.forename: Karelia
authors.initials: K
authors.lastname: Cosme
authors.forename: Jorge V
authors.initials: JV
authors.lastname: Gavilondo
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D008297:Male; D009369:Neoplasms / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D007074:Immunoglobulin G; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A