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OX40L blockade and allergen-induced airway responses in subjects with mild asthma.


ABSTRACT: The OX40/OX40L interaction contributes to an optimal T cell response following allergic stimuli and plays an important role in the maintenance and reactivation of memory T effector cells.We tested whether treatment with an anti-OX40L monoclonal antibody (MAb) would inhibit allergen-induced responses in subjects with asthma.Twenty-eight mild, atopic asthmatic subjects were recruited for a double-blind, randomized, placebo-controlled, parallel-group trial (ClinicalTrials.gov identifier NCT00983658) to compare blockade of OX40L using a humanized anti-OX40L MAb to placebo-administered intravenously in 4 doses over 3 months. Allergen inhalation challenges were carried out 56 and 113 days after the first dose of study drug. The primary outcome variable was the late-phase asthmatic response. Other outcomes included the early-phase asthmatic response, airway hyperresponsiveness, serum IgE levels, blood and sputum eosinophils, safety and tolerability.Treatment with anti-OX40L MAb did not attenuate the early- or late-phase asthmatic responses at days 56 or 113 compared with placebo. In the anti-OX40L MAb treatment group, total IgE was reduced 17% from pre-dosing levels, and sputum eosinophils decreased 75% by day 113 (both P = 0.04). There was no effect of anti-OX40L MAb on airway hyperresponsiveness or blood eosinophils. The frequency of AEs was similar in both groups.Pharmacological activity of anti-OX40L MAb was observed by decreases in serum total IgE and airway eosinophils at 16 weeks post-dosing, but there was no effect on allergen-induced airway responses. It is possible that the treatment duration or dose of antibody was insufficient to impact the airway responses.

SUBMITTER: Gauvreau GM 

PROVIDER: S-EPMC4253735 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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OX40L blockade and allergen-induced airway responses in subjects with mild asthma.

Gauvreau G M GM   Boulet L-P LP   Cockcroft D W DW   FitzGerald J M JM   Mayers I I   Carlsten C C   Laviolette M M   Killian K J KJ   Davis B E BE   Larché M M   Kipling C C   Dua B B   Mosesova S S   Putnam W W   Zheng Y Y   Scheerens H H   McClintock D D   Matthews J G JG   O'Byrne P M PM  

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 20140101 1


<h4>Background</h4>The OX40/OX40L interaction contributes to an optimal T cell response following allergic stimuli and plays an important role in the maintenance and reactivation of memory T effector cells.<h4>Objective</h4>We tested whether treatment with an anti-OX40L monoclonal antibody (MAb) would inhibit allergen-induced responses in subjects with asthma.<h4>Methods</h4>Twenty-eight mild, atopic asthmatic subjects were recruited for a double-blind, randomized, placebo-controlled, parallel-g  ...[more]

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