Therapeutic antibodies elicited by immunization against TNF-α

• Published in: Nature biotechnology Vol. 17; no. 7; pp. 666 - 669
• Main Authors: Mouritsen, Søren, Dalum, Iben, Butler, Debra M, Jensen, Martin R, Hindersson, Peter, Steinaa, Lucilla, Waterston, Ashita M, Grell, Susanne N, Feldmann, Marc, Elsner, Henrik I
• Format: Journal Article
• Language: English
• Published: New York, NY Nature 01-07-1999
• Subjects: Animals; Arthritis, Rheumatoid - chemically induced; Arthritis, Rheumatoid - therapy; Autoantibodies - blood; Biological and medical sciences; Biotechnology; Cachexia - immunology; Cachexia - therapy; Collagen - immunology; Epitopes; Fundamental and applied biological sciences. Psychology; Health. Pharmaceutical industry; Immunization; Industrial applications and implications. Economical aspects; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred DBA; Neutralization Tests; Production of active biomolecules; Recombinant Proteins - immunology; T-Lymphocytes - immunology; Tumor Necrosis Factor-alpha - immunology; Vaccins; Animal model; Antigenic determinant; Vaccination; Rodentia; Cytokine; Autoantibody; Immunodominance; Active immunization; Inflammatory disease; Vertebrata; Mammalia; Mouse; Mutation; Recombinant protein; Tumor necrosis factor α
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/10878

Tumor necrosis factor-alpha (TNF-alpha) is critically involved in the pathogenesis of several chronic inflammatory diseases. Monoclonal antibodies against TNF-alpha 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-alpha. This vaccination approach leads to a T-cell-dependent polyclonal and sustainable anti-TNF-alpha autoantibody response that declines upon discontinuation of booster injections. The autoantibodies are elicited by injecting modified recombinant TNF-alpha 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-alpha may be a useful approach for the treatment of rheumatoid arthritis and other chronic inflammatory diseases.