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
| Autor: | Tatjana Bozanovic, William E. Carson, Megan J. Miller, Kevin Chu Foy, Nicanor Moldovan, Pravin T. P. Kaumaya |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Angiogenesis
medicine.medical_treatment Immunology Pharmacology chemoagents epitopes Metastasis angiogenesis paclitaxel 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Trastuzumab medicine Immunology and Allergy 030304 developmental biology 0303 health sciences Cardiotoxicity Chemotherapy VEGF peptide mimics business.industry toxicity Cancer Immunotherapy medicine.disease 3. Good health HER-2 peptide mimics Oncology Paclitaxel chemistry peptidomimetics 030220 oncology & carcinogenesis immunotherapy monoclonal antibodies business Research Paper medicine.drug |
| Zdroj: | Oncoimmunology |
| ISSN: | 2162-402X |
| DOI: | 10.4161/onci.21057 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|