Peptide vaccines and peptidomimetics of EGFR (HER-1) ligand binding domain inhibit cancer cell growth in vitro and in vivo

Kevin Chu Foy, Ruthie M. Wygle, Megan J. Miller, Jay P. Overholser, Tanios Bekaii-Saab, Pravin T.P. Kaumaya

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Epidermal growth factor receptor (EGFR) is a validated target for several cancers including lung, colorectal, and certain subtypes of breast cancer. Cetuximab targets ligand binding of EGFR, but major problems like high cost, short t1/2, toxicity, and emergence of resistance are associated with the drug. Immunization with EGFR B cell epitopes will train the immune system to produce specific Abs that can kill cancer cells. Also, therapy with stable, less-expensive, and nontoxic EGFR peptide mimics will block EGFR signaling and inhibit cancer growth. We designed three peptides based on the contact sites between EGF and EGFR. The B cell epitopes were synthesized alone and also linked with the measles virus T cell epitope to produce a chimeric peptide vaccine. The peptide vaccines were immunogenic in both mice and rabbits and Abs raised against the vaccine specifically bound EGFRexpressing cells and recombinant human EGFR protein. The peptide mimics and the anti-peptide Abs were able to inhibit EGFR signaling pathways. Immunization with the peptide vaccine or treatment with the B cell epitopes significantly reduced tumor growth in both transplantable breast and lung cancer models. Immunohistochemical analysis also showed significant reductions in microvascular density and actively dividing cells in the tumor sections after treatment in the FVB/n breast cancer model. The 418- 435 B cell epitope was the best candidate both as a vaccine or peptide mimic because it caused significant inhibition in the two mouse models. Our results show that this novel EGFR B cell epitope has great potential to be used as a vaccine or treatment option for EGFR-expressing cancers.

Original languageEnglish (US)
Pages (from-to)217-227
Number of pages11
JournalJournal of Immunology
Volume191
Issue number1
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

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Peptidomimetics
Subunit Vaccines
Epidermal Growth Factor Receptor
Ligands
B-Lymphocyte Epitopes
Growth
Neoplasms
Peptides
Breast Neoplasms
Immunization
Lung Neoplasms
Vaccines
In Vitro Techniques
Measles virus
T-Lymphocyte Epitopes
Therapeutics
Epidermal Growth Factor
Immune System
Rabbits

ASJC Scopus subject areas

  • Immunology

Cite this

Peptide vaccines and peptidomimetics of EGFR (HER-1) ligand binding domain inhibit cancer cell growth in vitro and in vivo. / Foy, Kevin Chu; Wygle, Ruthie M.; Miller, Megan J.; Overholser, Jay P.; Bekaii-Saab, Tanios; Kaumaya, Pravin T.P.

In: Journal of Immunology, Vol. 191, No. 1, 01.07.2013, p. 217-227.

Research output: Contribution to journalArticle

Foy, Kevin Chu ; Wygle, Ruthie M. ; Miller, Megan J. ; Overholser, Jay P. ; Bekaii-Saab, Tanios ; Kaumaya, Pravin T.P. / Peptide vaccines and peptidomimetics of EGFR (HER-1) ligand binding domain inhibit cancer cell growth in vitro and in vivo. In: Journal of Immunology. 2013 ; Vol. 191, No. 1. pp. 217-227.
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