PMID- 25941588
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20210218
LR  - 20210218
IS  - 2162-4011 (Print)
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Linking)
VI  - 3
IP  - 11
DP  - 2014 Nov
TI  - HER-3 peptide vaccines/mimics: Combined therapy with IGF-1R, HER-2, and HER-1 
      peptides induces synergistic antitumor effects against breast and pancreatic 
      cancer cells.
PG  - e956012
LID - e956012
AB  - The human epidermal growth factor receptor 3 (HER-3/ErbB3) is a unique member of 
      the human epidermal growth factor family of receptors, because it lacks intrinsic 
      kinase activity and ability to heterodimerize with other members. HER-3 is 
      frequently upregulated in cancers with epidermal growth factor receptor 
      (EGFR/HER-1/ErbB1) or human epidermal growth factor receptor 2 (HER-2/ErBB2) 
      overexpression, and targeting HER-3 may provide a route for overcoming resistance 
      to agents that target EGFR or HER-2. We have previously developed vaccines and 
      peptide mimics for HER-1, HER-2 and vascular endothelial growth factor (VEGF). In 
      this study, we extend our studies by identifying and evaluating novel HER-3 
      peptide epitopes encompassing residues 99-122, 140-162, 237-269 and 461-479 of 
      the HER-3 extracellular domain as putative B-cell epitopes for active 
      immunotherapy against HER-3 positive cancers. We show that the HER-3 vaccine 
      antibodies and HER-3 peptide mimics induced antitumor responses: inhibition of 
      cancer cell proliferation, inhibition of receptor phosphorylation, induction of 
      apoptosis and antibody dependent cellular cytotoxicity (ADCC). Two of the HER-3 
      epitopes 237-269 (domain II) and 461-479 (domain III) significantly inhibited 
      growth of xenografts originating from both pancreatic (BxPC3) and breast (JIMT-1) 
      cancers. Combined therapy of HER-3 (461-471) epitope with HER-2 (266-296), HER-2 
      (597-626), HER-1 (418-435) and insulin-like growth factor receptor type I 
      (IGF-1R) (56-81) vaccine antibodies and peptide mimics show enhanced antitumor 
      effects in breast and pancreatic cancer cells. This study establishes the 
      hypothesis that combination immunotherapy targeting different signal transduction 
      pathways can provide effective antitumor immunity and long-term control of HER-1 
      and HER-2 overexpressing cancers.
FAU - Miller, Megan Jo
AU  - Miller MJ
AD  - Department of Microbiology; The Ohio State University , Columbus, OH USA.
FAU - Foy, Kevin C
AU  - Foy KC
AD  - Department of Obstetrics and Gynecology; The Ohio State University Wexner Medical 
      Center ; Columbus, OH USA.
FAU - Overholser, Jay P
AU  - Overholser JP
AD  - Department of Obstetrics and Gynecology; The Ohio State University Wexner Medical 
      Center ; Columbus, OH USA.
FAU - Nahta, Rita
AU  - Nahta R
AD  - Department of Pharmacology; Emory University , Atlanta, GA USA.
FAU - Kaumaya, Pravin Tp
AU  - Kaumaya PT
AD  - Department of Microbiology; The Ohio State University , Columbus, OH USA ; 
      Department of Obstetrics and Gynecology; The Ohio State University Wexner Medical 
      Center ; Columbus, OH USA ; The James Cancer Hospital and Solove Research 
      Institute; and the Comprehensive Cancer Center; The Ohio State University , 
      Columbus, OH USA.
LA  - eng
GR  - R01 CA157754/CA/NCI NIH HHS/United States
GR  - R01 CA084356/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141221
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
PMC - PMC4368151
OTO - NOTNLM
OT  - ADCC, antibody dependent, cellular cytotoxicity
OT  - Antibodies
OT  - ECD, extracellular domain
OT  - ELISA, enzyme-linked immunosorbent assay
OT  - FDA, Federal Drug Administration
OT  - HER-1
OT  - HER-1 (EGFR or ErbB1), human epidermal growth factor receptor
OT  - HER-2
OT  - HER-2 (ErbB2), human epidermal growth factor receptor 2
OT  - HER-3 (ErbB3), human epidermal growth factor receptor 3
OT  - HER-3 (erbb3)
OT  - HER-4 (ErbB4), human epidermal growth factor receptor 4
OT  - HPLC, high-pressure liquid chromatography
OT  - IGF-1R
OT  - Immunotherapy
OT  - MALDI, matrix-assisted laser desorption/ionization
OT  - MVF, Measles virus fusion protein
OT  - RTK, receptor tyrosine kinase
OT  - TKIs, Tyrosine kinase inhibitors.
OT  - immunogenicity
OT  - mAb, monocolonal antibody
OT  - peptide vaccines
OT  - peptidomimetics
OT  - receptor tyrosine kinases
EDAT- 2015/05/06 06:00
MHDA- 2015/05/06 06:01
PMCR- 2015/12/17
CRDT- 2015/05/06 06:00
PHST- 2014/07/08 00:00 [received]
PHST- 2014/08/14 00:00 [accepted]
PHST- 2015/05/06 06:00 [entrez]
PHST- 2015/05/06 06:00 [pubmed]
PHST- 2015/05/06 06:01 [medline]
PHST- 2015/12/17 00:00 [pmc-release]
AID - 956012 [pii]
AID - 10.4161/21624011.2014.956012 [doi]
PST - epublish
SO  - Oncoimmunology. 2014 Dec 21;3(11):e956012. doi: 10.4161/21624011.2014.956012. 
      eCollection 2014 Nov.