Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model

MAbs
Jonathan NambiarAnthony G Doyle

Abstract

CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor β-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor β-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 r...Continue Reading

References

Jul 7, 1997·The Journal of Experimental Medicine·M ExleyS Porcelli
Mar 6, 2002·The Journal of Experimental Medicine·Peter T LeeAlbert Bendelac
Aug 7, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mariette LisbonneMaria C Leite-de-Moraes
Jul 13, 2005·The Journal of Experimental Medicine·Elisabetta AgeaFabrizio Spinozzi
Aug 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Simon C YueMark A Exley
Mar 17, 2006·The New England Journal of Medicine·Omid AkbariDale T Umetsu
Apr 4, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Weiming YuanPeter Cresswell
Apr 10, 2009·The Journal of Allergy and Clinical Immunology·Ponpan MatangkasombutDale T Umetsu
Jul 1, 2009·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Sufi R MorshedSamuel Strober
Sep 23, 2009·Mutation Research·Jenna R Murdoch, Clare M Lloyd
Dec 19, 2009·American Journal of Respiratory and Critical Care Medicine·Triya DamayantiToshihiro Nukiwa
Jun 1, 2011·The Journal of Experimental Medicine·Gerhard WingenderAnthony A Horner
Sep 21, 2011·The Journal of Experimental Medicine·Seth T ScanlonAlbert Bendelac
Nov 1, 2011·Nature Immunology·Patrick J BrennanMichael B Brenner
Nov 17, 2012·Nature Reviews. Immunology·Jamie RossjohnDale I Godfrey
Dec 26, 2012·The Journal of Allergy and Clinical Immunology·Beatriz Abós-GraciaEduardo Martínez-Naves

❮ Previous
Next ❯

Citations

Mar 2, 2016·Annual Review of Immunology·Lucia MoriGennaro De Libero
May 5, 2017·British Journal of Pharmacology·Tin KyawAlex Bobik
Sep 14, 2018·Frontiers in Immunology·Chiaki Iwamura, Toshinori Nakayama

❮ Previous
Next ❯

Methods Mentioned

BETA
enzyme-linked
electrophoresis
bronchoalveolar lavage
lavage
phage display
surface plasmon resonance
ELISA
flow cytometry
X-ray
flow

Software Mentioned

GraphPad Prism
Biacore T200
EMKA

Related Concepts

Related Feeds

Asthma

This feed focuses in Asthma in which your airways narrow and swell. This can make breathing difficult and trigger coughing, wheezing and shortness of breath.

Ascariasis (ASM)

Ascariasis is a helminthic infection of global distribution with more than 1.4 billion persons infected throughout the world. Here is the latest research.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Basophils

Basophils are myeloid cells with a high affinity IgE receptor and is involved in inflammatory responses during allergy. Discover the latest research on Basophils here.

Ascariasis

Ascariasis is a helminthic infection of global distribution with more than 1.4 billion persons infected throughout the world. Here is the latest research.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

© 2022 Meta ULC. All rights reserved