Induction of TNF-α Autoantibody Production by AutoVac TNF106: A Novel Therapeutic Approach for the Treatment of Allergic Diseases

Background: Cytokines play an integral role in the coordination and persistence of allergic inflammatory processes and therefore represent prime targets for novel therapies in diseases such as asthma. Multiple attempts to generate low-molecular-weight cytokine inhibitors have failed, and the main attention has focused on the development of biological agents such as neutralizing antibodies. The present work describes a simple and effective method to induce the production of therapeutic anti-cytokine autoantibodies by active immunization against a modified endogenous cytokine. Methods: Balb/c mice were subcutaneously injected with AutoVac TNF106, a recombinant murine TNF-α molecule containing a foreign immunogenic T helper epitope, and the induction of neutralizing anti-TNF-α autoantibodies was analysed. These mice were then sensitized with ovalbumin (OVA), and the effect of neutralizing anti-TNF-α autoantibodies on the allergen-induced airway inflammation was analysed. Results: AutoVac TNF106-immunized mice developed high titres of neutralizing anti-TNF-α autoantibodies, which were maintained for at least 4 weeks after the last booster injection. Mice vaccinated with AutoVac TNF106 and further immunized against OVA showed diminished TNF-α levels in the bronchoalveolar lavage (BAL) fluid after OVA challenge. Moreover, pretreatment with AutoVac TNF106 resulted in significantly reduced numbers of eosinophils and neutrophils in BAL fluid in response to single or multiple allergen exposure. Conclusion: The induction of anti-TNF-α autoantibody production by the AutoVac TNF106 technology not only confirmed the role of TNF-α in the induction of allergic inflammation but also offers a novel approach to block the activity of cytokines in order to treat allergic inflammatory conditions.