Combination Treatment with Her-2 and VEGF Peptide Mimics Induces Potent Anti-Tumor and Anti-Angiogenic Responses In Vitro and In Vivo

摘要

HER-2 is a member of the EGFR family and is overexpressed in 20-30% of breast cancers. HER-2 overexpression causes increased expression of VEGF at both the RNA and protein level [1]. These two proteins are therefore considered good targets for cancer treatment which have led to the development of two humanized monoclonal antibodies (mAb) Pertuzumab and Bevacizumab that target HER-2 and VEGF respectively. Exposure of HER-2 overexpressing cells to trastuzumab/herceptin another mAb that targets HER-2 significantly decreases VEGF expression [2]. Although passive immunotherapy with these Abs has been approved for treatment of advanced breast cancer, a number of concerns exist with passive immunotherapy. Treatment is expensive, and has a limited duration of action, necessitating repeated administrations of the mAb. Peptide therapy with conformational B-cell epitope mimics can be cheaper with a longer half-life. The goal of the present study was to show that combination treatment with HER-2 and VEGF peptide mimics provides greater efficacy than single treatment. We designed and synthesized peptides based on the binding of (i) HER-2 with Pertuzumab and (ii) VEGF with VEGFR2. We show that combination treatment with these peptides induces potent anti-tumor and anti-angiogenic responses in vitro and in vivo.