PMID- 24990880
OWN - NLM
STAT- MEDLINE
DCOM- 20150223
LR  - 20140703
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Linking)
VI  - 6
IP  - 243
DP  - 2014 Jul 2
TI  - Targeting membrane-expressed IgE B cell receptor with an antibody to the M1 prime 
      epitope reduces IgE production.
PG  - 243ra85
LID - 10.1126/scitranslmed.3008961 [doi]
AB  - Elevated serum levels of both total and allergen-specific immunoglobulin E (IgE) 
      correlate with atopic diseases such as allergic rhinitis and allergic asthma. 
      Neutralization of IgE by anti-IgE antibodies can effectively treat allergic 
      asthma. Preclinical studies indicate that targeting membrane IgE-positive cells 
      with antibodies against M1 prime can inhibit the production of new IgE and 
      significantly reduce the levels of serum IgE. We report results from two trials 
      that investigated the safety, pharmacokinetics, and activity of quilizumab, a 
      humanized monoclonal antibody targeting specifically the M1 prime epitope of 
      membrane IgE, in subjects with allergic rhinitis (NCT01160861) or mild allergic 
      asthma (NCT01196039). In both studies, quilizumab treatment was well tolerated 
      and led to reductions in total and allergen-specific serum IgE that lasted for at 
      least 6 months after the cessation of dosing. In subjects with allergic asthma 
      who were subjected to an allergen challenge, quilizumab treatment blocked the 
      generation of new IgE, reduced allergen-induced early and late asthmatic airway 
      responses by 26 and 36%, respectively, and reduced allergen-induced increases in 
      sputum eosinophils by ~50% compared with placebo. These studies indicate that 
      targeting of membrane IgE-expressing cells with anti-M1 prime antibodies can 
      prevent IgE production in humans.
CI  - Copyright (c) 2014, American Association for the Advancement of Science.
FAU - Gauvreau, Gail M
AU  - Gauvreau GM
AD  - McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
FAU - Harris, Jeffrey M
AU  - Harris JM
AD  - Genentech Inc., South San Francisco, CA 94080, USA. harris.jeffrey@gene.com.
FAU - Boulet, Louis-Philippe
AU  - Boulet LP
AD  - Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec, Quebec 
      G1V 4G5, Canada.
FAU - Scheerens, Heleen
AU  - Scheerens H
AD  - Genentech Inc., South San Francisco, CA 94080, USA.
FAU - Fitzgerald, J Mark
AU  - Fitzgerald JM
AD  - University of British Columbia, Vancouver, British Columbia V5Z 1M9, Canada.
FAU - Putnam, Wendy S
AU  - Putnam WS
AD  - Genentech Inc., South San Francisco, CA 94080, USA.
FAU - Cockcroft, Donald W
AU  - Cockcroft DW
AD  - University of Saskatchewan, Saskatoon, Saskatchewan S7N 0W8, Canada.
FAU - Davis, Beth E
AU  - Davis BE
AD  - University of Saskatchewan, Saskatoon, Saskatchewan S7N 0W8, Canada.
FAU - Leigh, Richard
AU  - Leigh R
AD  - University of Calgary, Calgary, Alberta T2N 4Z6, Canada.
FAU - Zheng, Yanan
AU  - Zheng Y
AD  - Genentech Inc., South San Francisco, CA 94080, USA.
FAU - Dahlen, Barbro
AU  - Dahlen B
AD  - Karolinska University Hospital, Stockholm S-141 86, Sweden.
FAU - Wang, Yehong
AU  - Wang Y
AD  - Genentech Inc., South San Francisco, CA 94080, USA.
FAU - Maciuca, Romeo
AU  - Maciuca R
AD  - Genentech Inc., South San Francisco, CA 94080, USA.
FAU - Mayers, Irvin
AU  - Mayers I
AD  - University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
FAU - Liao, X Charlene
AU  - Liao XC
AD  - Genentech Inc., South San Francisco, CA 94080, USA.
FAU - Wu, Lawren C
AU  - Wu LC
AD  - Genentech Inc., South San Francisco, CA 94080, USA.
FAU - Matthews, John G
AU  - Matthews JG
AD  - Genentech Inc., South San Francisco, CA 94080, USA.
FAU - O'Byrne, Paul M
AU  - O'Byrne PM
AD  - McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
LA  - eng
SI  - ClinicalTrials.gov/NCT01160861
SI  - ClinicalTrials.gov/NCT01196039
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (Epitopes)
RN  - 0 (Receptors, IgE)
RN  - 0 (anti-IgE antibodies)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Adult
MH  - Antibodies, Anti-Idiotypic/*immunology/*therapeutic use
MH  - Epitopes/*immunology
MH  - Female
MH  - Humans
MH  - Immunoglobulin E/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Receptors, IgE/antagonists & inhibitors/*immunology
EDAT- 2014/07/06 06:00
MHDA- 2015/02/24 06:00
CRDT- 2014/07/04 06:00
PHST- 2014/07/04 06:00 [entrez]
PHST- 2014/07/06 06:00 [pubmed]
PHST- 2015/02/24 06:00 [medline]
AID - 6/243/243ra85 [pii]
AID - 10.1126/scitranslmed.3008961 [doi]
PST - ppublish
SO  - Sci Transl Med. 2014 Jul 2;6(243):243ra85. doi: 10.1126/scitranslmed.3008961.