PMID- 29650949
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20190412
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 9
IP  - 1
DP  - 2018 Apr 12
TI  - Treating cat allergy with monoclonal IgG antibodies that bind allergen and 
      prevent IgE engagement.
PG  - 1421
LID - 10.1038/s41467-018-03636-8 [doi]
LID - 1421
AB  - Acute allergic symptoms are caused by allergen-induced crosslinking of 
      allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on 
      effector cells. Desensitization with allergen-specific immunotherapy (SIT) has 
      been used for over a century, but the dominant protective mechanism remains 
      unclear. One consistent observation is increased allergen-specific IgG, thought 
      to competitively block allergen binding to IgE. Here we show that the blocking 
      potency of the IgG response to Cat-SIT is heterogeneous. Next, using two potent, 
      pre-selected allergen-blocking monoclonal IgG antibodies against the 
      immunodominant cat allergen Fel d 1, we demonstrate that increasing the IgG/IgE 
      ratio reduces the allergic response in mice and in cat-allergic patients: a 
      single dose of blocking IgG reduces clinical symptoms in response to nasal 
      provocation (ANCOVA, p = 0.0003), with a magnitude observed at day 8 similar to 
      that reported with years of conventional SIT. This study suggests that simply 
      augmenting the blocking IgG/IgE ratio may reverse allergy.
FAU - Orengo, J M
AU  - Orengo JM
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA. jamie.orengo@regeneron.com.
FAU - Radin, A R
AU  - Radin AR
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Kamat, V
AU  - Kamat V
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Badithe, A
AU  - Badithe A
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Ben, L H
AU  - Ben LH
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Bennett, B L
AU  - Bennett BL
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Zhong, S
AU  - Zhong S
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Birchard, D
AU  - Birchard D
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Limnander, A
AU  - Limnander A
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Rafique, A
AU  - Rafique A
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Bautista, J
AU  - Bautista J
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Kostic, A
AU  - Kostic A
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Newell, D
AU  - Newell D
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Duan, X
AU  - Duan X
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Franklin, M C
AU  - Franklin MC
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Olson, W
AU  - Olson W
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Huang, T
AU  - Huang T
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Gandhi, N A
AU  - Gandhi NA
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Lipsich, L
AU  - Lipsich L
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Stahl, N
AU  - Stahl N
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Papadopoulos, N J
AU  - Papadopoulos NJ
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Murphy, A J
AU  - Murphy AJ
AUID- ORCID: 0000-0003-4152-4081
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
FAU - Yancopoulos, G D
AU  - Yancopoulos GD
AD  - Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 
      10591, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180412
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Allergens)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Complex Mixtures)
RN  - 0 (Glycoproteins)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, IgE)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - G408EE88II (Fel d 1 protein, Felis domesticus)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Allergens/administration & dosage/immunology/isolation & purification
MH  - Animal Fur/chemistry/immunology
MH  - Animals
MH  - Antibodies, Monoclonal/biosynthesis/*pharmacology
MH  - Binding, Competitive
MH  - Cats
MH  - Complex Mixtures/chemistry/immunology
MH  - Desensitization, Immunologic/*methods
MH  - Disease Models, Animal
MH  - Female
MH  - Glycoproteins/administration & dosage/*immunology/isolation & purification
MH  - Humans
MH  - Hypersensitivity/immunology/physiopathology/*therapy
MH  - Immunoglobulin E/chemistry/immunology/metabolism
MH  - Immunoglobulin G/biosynthesis/*pharmacology
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Protein Binding/drug effects
MH  - Receptors, IgE/chemistry/*immunology/metabolism
PMC - PMC5897525
COIS- All authors are employees of Regeneron Pharmaceuticals, Inc, and may hold stock 
      and/or stock options in the company.
EDAT- 2018/04/14 06:00
MHDA- 2018/11/27 06:00
PMCR- 2018/04/12
CRDT- 2018/04/14 06:00
PHST- 2017/07/05 00:00 [received]
PHST- 2018/02/23 00:00 [accepted]
PHST- 2018/04/14 06:00 [entrez]
PHST- 2018/04/14 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2018/04/12 00:00 [pmc-release]
AID - 10.1038/s41467-018-03636-8 [pii]
AID - 3636 [pii]
AID - 10.1038/s41467-018-03636-8 [doi]
PST - epublish
SO  - Nat Commun. 2018 Apr 12;9(1):1421. doi: 10.1038/s41467-018-03636-8.