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

Clin Exp Allergy. 2014 Jan;44(1):29-37. doi: 10.1111/cea.12235.


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.

Keywords: allergen inhalation challenge; anti-OX40L; mild atopic asthma; proof-of-activity.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Allergens / immunology*
  • Anti-Asthmatic Agents / adverse effects
  • Anti-Asthmatic Agents / pharmacology
  • Anti-Asthmatic Agents / therapeutic use*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / immunology*
  • Asthma / metabolism
  • CD40 Antigens / metabolism
  • CD40 Ligand / antagonists & inhibitors*
  • CD40 Ligand / metabolism
  • Dendritic Cells / immunology
  • Eosinophils
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Leukocyte Count
  • Male
  • Middle Aged
  • Signal Transduction / drug effects
  • T-Lymphocytes / immunology
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Allergens
  • Anti-Asthmatic Agents
  • Antibodies, Monoclonal
  • CD40 Antigens
  • CD40 Ligand
  • Immunoglobulin E

Associated data

  • ClinicalTrials.gov/NCT00983658