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)

Jay Overholser, Kristen Henkins Ambegaokar, Siobhan M. Eze, Eduardo Sanabria-Figueroa, Rita Nahta, Tanios Bekaii-Saab, Pravin T.P. Kaumaya

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)519-543
Number of pages25
JournalVaccines
Volume3
Issue number3
DOIs
StatePublished - Jun 30 2015
Externally publishedYes

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Keywords

  • Antibodies
  • Epitopes
  • Immunogenicity
  • Peptide mimics
  • Peptide vaccines
  • Resistance
  • Vaccine candidates

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

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