Anti-Tumor Effects of Peptide Therapeutic and Peptide Vaccine Antibody Co-targeting HER-1 and HER-2 in Esophageal Cancer (EC) and HER-1 and IGF-1R in Triple-Negative Breast Cancer (TNBC).

• Type of Material: Article
• Authors: Jay Overholser, The Ohio State University Wexner Medical Center; Kristen Henkins Ambegaokar, The Ohio State University Wexner Medical Center; Siobhan M. Eze, Emory University; Eduardo Sanabria-Figueroa, Emory University; Rita Nahta, Emory University; Tanios Bekaii-Saab, The Ohio State University; Pravin T.P. Kaumaya, The Ohio State University Wexner Medical Center
• Language: English
• Date: 2015
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2015 by the authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/vaccines3030519
• Title of Journal or Parent Work: Vaccines
• ISSN: 2076-393X
• Volume: 3
• Issue: 3
• Start Page: 519
• End Page: 543
• Grant/Funding Information: This work was supported by funding from NIH R01 CA 84356 (PTPK), OSU Peptide Research Fund (PTPK).
• Keywords: vaccine candidates; peptide mimics; antibodies; peptide vaccines; resistance; immunogenicity; epitopes
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Oncology

Abstract

Despite the promise of targeted therapies, there remains an urgent need for effective treatment for esophageal cancer (EC) and triple-negative breast cancer (TNBC). Current FDA-approved drugs have significant problems of toxicity, safety, selectivity, efficacy and development of resistance. In this manuscript, we demonstrate that rationally designed peptide vaccines/mimics are a viable therapeutic strategy for blocking aberrant molecular signaling pathways with high affinity, specificity, potency and safety. Specifically, we postulate that novel combination treatments targeting members of the EGFR family and IGF-1R will yield significant anti-tumor effects in in vitro models of EC and TNBC possibly overcoming mechanisms of resistance. We show that the combination of HER-1 and HER-2 or HER-1 and IGF-1R peptide mimics/vaccine antibodies exhibited enhanced antitumor properties with significant inhibition of tumorigenesis in OE19 EC and MDA-MB-231 TNBC cell lines. Our work elucidates the mechanisms of HER-1/IGF-1R and HER-1/HER-2 signaling in these cancer cell lines, and the promising results support the rationale for dual targeting with HER-1 and HER-2 or IGF-1R as an improved treatment regimen for advanced therapy tailored to difference types of cancer.