CIGB-247 vaccine breaks immunological tolerance to the vascular endothelial growth factor in mice, rats, rabbits and non-human primates, without disturbing physiologic angiogenic processes
Abstract
CIGB-247 is a novel cancer therapeutic vaccine that uses a mutated form of 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). The vaccine was designed to affect tumor neo-vascularization and tumor cell viability by eliciting antibodies that block the interaction of VEGF and its receptors in activated endothelial cells, as well as specific cytotoxic T cells that can directly destroy tumor and tumor stroma cells producing VEGF. Our previous experimental studies with CIGB-247 in mice, in which VEGF shares an 87% homology to the human molecule, have shown that the vaccine has anti-tumoral and anti-metastatic activity, and produces anti-VEGF antibodies and a specific T cell cytotoxic response against tumor cells. Herein we extend the immunogenicity and safety studies of CIGB-247 in mice, rats, rabbits and non-human primates. All the species develop antigen-specific IgG antibodies able to block the interaction of VEGF and VEGF receptor 2 in an ELISA assay. Purified IgG from CIGB-247 immunized monkey sera effectively impair human microvascular endothelial cells' proliferation and capillary-like structures formation in MatrigelTM. In monkeys and mice, DTH and direct cell cytotoxicity experiments suggest that specific T cell responses are elicited after vaccination. Immunization with CIGB-247 does not affect animal behavior, hematology counts, blood biochemistry or histology of critical organs. Skin deep wound healing was not affected in vaccinated rats and monkeys. Altogether, these results support further clinical development of CIGB-247 therapeutic cancer vaccine, and shed light on the potential mechanisms underlying its effects.
