title: Immunotherapy with HER-2 and VEGF peptide mimics plus metronomic paclitaxel causes superior antineoplastic effects in transplantable and transgenic mouse models of human breast cancer.
abstract: HER-2 and the vascular endothelial factor receptor (VEGF) represent validated targets for the therapy of multiple tumor types and inhibitors of these receptors have gained increasing importance in the clinic. In this context, novel bioactive agents associated with better therapeutic outcomes and improved safety profile are urgently required. Specifically engineered HER-2- and VEGF-derived peptides in combination with low-dose chemotherapy might provide a substantial impact on tumor metastasis and cancer progression. We tested the antitumor effects of HER-2 and VEGF peptide mimics in combination with metronomic paclitaxel in both PyMT and Balb/c murine model challenged with TUBO cells. The combination of low-dose paclitaxel and HER-2 or VEGF peptide mimics had greater inhibitory effects than either agent alone. Peptide treatment caused virtually no cardiotoxic effects, while paclitaxel and the anti-HER-2 antibody trastuzumab (Herceptin), exerted consistent cardiotoxicity. The combination regimen also promoted significant reductions in tumor burden and prolonged survival rates in both transgenic and transplantable tumor models. Tumor weights were significantly reduced in mice treated with HER-2 peptides alone, and even more in animals that received HER-2 peptide with low-dose paclitaxel, which alone had no significant effects on tumor growth in the transgenic model. Specifically engineered native peptide sequences from HER-2 and VEGF used in combination with metronomic paclitaxel demonstrate enhanced anticancer efficacy and an encouraging safety profile. This novel approach to targeted therapy may offer new avenues for the treatment of breast cancer and other solid tumors that overexpress HER-2 and VEGF.
authors.affiliation: Department of Obstetrics and Gynecology; The Ohio State University Wexner Medical Center; Columbus, OH USA ; Department of Microbiology; The Ohio State University Wexner Medical Center; Columbus, OH USA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Foy
authors.affiliation: Department of Obstetrics and Gynecology; The Ohio State University Wexner Medical Center; Columbus, OH USA ; Department of Microbiology; The Ohio State University Wexner Medical Center; Columbus, OH USA.
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Miller
authors.affiliation: Department of Internal Medicine; The Ohio State University Wexner Medical Center; Columbus, OH USA.
authors.forename: Nicanor
authors.initials: N
authors.lastname: Moldovan
authors.affiliation: Department of Gynecology and Obstetrics; School of Medicine; University of Belgrade; Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Bozanovic
authors.affiliation: James Cancer Hospital and Solove Research Institute and the Comprehensive Cancer Center; The Ohio State University; Columbus, OH USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
authors.affiliation: Department of Obstetrics and Gynecology; The Ohio State University Wexner Medical Center; Columbus, OH USA ; Department of Microbiology; The Ohio State University Wexner Medical Center; Columbus, OH USA ; James Cancer Hospital and Solove Research Institute and the Comprehensive Cancer Center; The Ohio State University; Columbus, OH USA.
authors.forename: Pravin T P
authors.initials: PT
authors.lastname: Kaumaya