As strong as an OX or as weak as a kitten?
| Autor: | Christopher E. Brightling |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty proof-of-activity mild atopic asthma biology business.industry CD40 Ligand Immunology Antibodies Monoclonal Original Articles Allergens Asthma Kitten Endocrinology Internal medicine biology.animal allergen inhalation challenge medicine Humans Immunology and Allergy Female Anti-Asthmatic Agents anti-OX40L business |
| Zdroj: | Clinical and Experimental Allergy |
| ISSN: | 0954-7894 |
| DOI: | 10.1111/cea.12209 |
| Popis: | Background 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. Objective We tested whether treatment with an anti-OX40L monoclonal antibody (MAb) would inhibit allergen-induced responses in subjects with asthma. Methods 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. Results 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. |
| Databáze: | OpenAIRE |
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