OX40L blockade and allergen-induced airway responses in subjects with mild asthma
Article first published online: 20 DEC 2013
© 2013 The Authors Clinical & Experimental Allergy Published by John Wiley & Sons Ltd
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Clinical & Experimental Allergy
Volume 44, Issue 1, pages 29–37, January 2014
How to Cite
Clinical & Experimental Allergy, 2014 (44) 29–37., , , , , , , , , , , , , , , , , and .
- Issue published online: 20 DEC 2013
- Article first published online: 20 DEC 2013
- Accepted manuscript online: 14 NOV 2013 12:50AM EST
- Manuscript Accepted: 16 OCT 2013
- Manuscript Revised: 9 SEP 2013
- Manuscript Received: 10 JUN 2013
- Genentech Inc.,
- allergen inhalation challenge;
- mild atopic asthma;
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.
Conclusion and Clinical Relevance
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.