Therapeutic antibodies elicited by immunization against TNF-α

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Abstract
Tumor necrosis factor-alpha (TNF-α) is critically involved in the pathogenesis of several chronic inflammatory diseases. Monoclonal antibodies against TNF-α are currently used for the treatment of rheumatoid arthritis and Crohn's disease. This report describes a simple and effective method for active immunization against self TNF-α. This vaccination approach leads to a T-cell–dependent polyclonal and sustainable anti–TNF-α autoantibody response that declines upon discontinuation of booster injections. The autoantibodies are elicited by injecting modified recombinant TNF-α molecules containing foreign immunodominant T-helper epitopes. In mice immunized with such molecules, the symptoms of experimental cachexia and type II collagen-induced arthritis are ameliorated. These results suggest that vaccination against TNF-α may be a useful approach for the treatment of rheumatoid arthritis and other chronic inflammatory diseases.