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)

Vaccines
Jay P OverholserPravin T P Kaumaya

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 dif...Continue Reading

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Citations

Oct 14, 2016·Endocrine-related Cancer·Aleksandra M Ochnik, Robert C Baxter
Nov 22, 2016·Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus·Yao LinKe-Neng Chen
Feb 1, 2016·Chemical Science·Mariusz Skwarczynski, Istvan Toth
May 8, 2021·Frontiers in Immunology·Svetlana V Guryanova, Rahim M Khaitov

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Methods Mentioned

BETA
xenografts
xenograft
ELISA
protein assay
Assay
caspase
transgenic

Clinical Trials Mentioned

NCT02120911
NCT01376505

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