The vascular endothelial growth factor (VEGF) plays a central role in angiogenesis and immunosuppressive cascades inherent to tumor development. Success of drugs targeting this growth factor and their receptors signaling cascade built upon these facts. Such passive targeting of VEGF/VEGFR pathway had two major caveats: non-manageable side effects and the induction of resistance phenomena. To overcome some of these problems we design an active immunization approach based on the use of a functionally deficient VEGF 121 isoform as antigen. Herein we present preclinical and clinical development data of HeberSaVax vaccine (formerly known as CIGB-247).
Safety, antitumoral and immunological effects of HeberSaVax administration were analyzed in mouse, rats, rabbits, non-human primates and in two Phase I clinical trials. Formulations containing the adjuvants VSSP (Very Small Size Particles from Neisseria Meningitides) or Alum phosphate were used. Vaccine was administered once a week (VSSP) or bi-weekly (Alum Phosphate) for 8 weeks. Immune response was evaluated using direct and indirect ELISA methods and IFN-gamma ELISPOT.
HeberSaVax administration inhibits implantation and growth of tumors and metastases favoring a significant increase in animals’ survival. In mice, rats, rabbits and on non-human primates the vaccine administration result in non-toxic induction of sustained antibody titers that specifically neutralized VEGF binding to VEGF receptors. Immunizations also induce VEGF specific cell mediated cytotoxicity. A total of 80 patients were included in the phase I/Ib clinical trials. Results indicated: a good safety profile that allows combining the vaccine with the existing arsenal for cancer therapy; the induction of specific humoral and cellular responses despite the advance stage of patient’s tumors and; an unexpected long term immune responses after 4 years of continuous treatment. As part of the trials three complete responses, one partial response and four stable diseases have been documented.
Altogether these results encourage further development of HeberSaVax vaccine for cancer therapy. Henceforth, a total of four Phase II/III clinical trials are planned to start in 2018 in specific localizations.
RPCEC00000102 and RPCEC00000155
Center for Genetic Engineering and Biotechnology (CIGB)
Heber Biotec, and Chemo
All authors have declared no conflicts of interest.