PMID- 23698748
OWN - NLM
STAT- MEDLINE
DCOM- 20130916
LR  - 20211021
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 191
IP  - 1
DP  - 2013 Jul 1
TI  - Peptide vaccines and peptidomimetics of EGFR (HER-1) ligand binding domain 
      inhibit cancer cell growth in vitro and in vivo.
PG  - 217-27
LID - 10.4049/jimmunol.1300231 [doi]
AB  - 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 EGFR-expressing 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.
FAU - Foy, Kevin Chu
AU  - Foy KC
AD  - Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH 
      43210, USA.
FAU - Wygle, Ruthie M
AU  - Wygle RM
FAU - Miller, Megan J
AU  - Miller MJ
FAU - Overholser, Jay P
AU  - Overholser JP
FAU - Bekaii-Saab, Tanios
AU  - Bekaii-Saab T
FAU - Kaumaya, Pravin T P
AU  - Kaumaya PT
LA  - eng
GR  - P30 CA016058/CA/NCI NIH HHS/United States
GR  - 84356/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130522
PL  - England
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes, B-Lymphocyte)
RN  - 0 (Ligands)
RN  - 0 (Peptidomimetics)
RN  - 0 (Vaccines, Subunit)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Cancer Vaccines/*administration & dosage/*immunology/metabolism
MH  - Cell Line, Tumor
MH  - Epitopes, B-Lymphocyte/administration & dosage/immunology/metabolism
MH  - ErbB Receptors/administration & dosage/antagonists & inhibitors/*metabolism
MH  - Humans
MH  - Ligands
MH  - Lung Neoplasms/immunology/*pathology/*prevention & control
MH  - Mammary Neoplasms, Experimental/immunology/*pathology/*prevention & control
MH  - Mice
MH  - *Peptidomimetics
MH  - Phosphorylation/immunology
MH  - Protein Binding/immunology
MH  - Protein Structure, Tertiary
MH  - Rabbits
MH  - Signal Transduction/immunology
MH  - Vaccines, Subunit/administration & dosage/immunology/metabolism
PMC - PMC4324564
MID - NIHMS648412
COIS- Disclosures The authors have no financial conflicts of interest.
EDAT- 2013/05/24 06:00
MHDA- 2013/09/17 06:00
PMCR- 2015/02/11
CRDT- 2013/05/24 06:00
PHST- 2013/05/24 06:00 [entrez]
PHST- 2013/05/24 06:00 [pubmed]
PHST- 2013/09/17 06:00 [medline]
PHST- 2015/02/11 00:00 [pmc-release]
AID - jimmunol.1300231 [pii]
AID - 10.4049/jimmunol.1300231 [doi]
PST - ppublish
SO  - J Immunol. 2013 Jul 1;191(1):217-27. doi: 10.4049/jimmunol.1300231. Epub 2013 May 
      22.