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).
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.
Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. jay.overholser@osumc.edu.
Jay
J
Overholser
Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. kristen.ambegaokar@osumc.edu.
Kristen Henkins
KH
Ambegaokar
Department of Pharmacology, Emory University and Winship Cancer Institute, Atlanta, GA 30322, USA. siobhan.maureen.donnelly@emory.edu.
Siobhan M
SM
Eze
Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322, USA. esanab2@emory.edu.
Eduardo
E
Sanabria-Figueroa
Department of Pharmacology, Emory University and Winship Cancer Institute, Atlanta, GA 30322, USA. esanab2@emory.edu.|Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322, USA. esanab2@emory.edu.
Rita
R
Nahta
James Cancer Hospital and Solove Research Institute and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. Tanios.Saab@osumc.edu.
Tanios
T
Bekaii-Saab
Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. Kaumaya.1@osu.edu.|James Cancer Hospital and Solove Research Institute and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. Kaumaya.1@osu.edu.
Pravin T P
PT
Kaumaya
antibodies; epitopes; immunogenicity; peptide mimics; peptide vaccines; resistance; vaccine candidates