Antigen dose escalation study of a VEGF-based therapeutic cancer vaccine in non human primates.

Summary of "Antigen dose escalation study of a VEGF-based therapeutic cancer vaccine in non human primates."

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 100μg, 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 100μg to 200 and 400μg/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.

Affiliation

Cancer Immunotherapy Laboratory, Department of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Playa Cubanacábn, Havana 10600, Cuba.

Journal Details

This article was published in the following journal.

Name: Vaccine
ISSN: 1873-2518
Pages: 368-77

Links

• PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22075086
• DOI: http://dx.doi.org/10.1016/j.vaccine.2011.10.082