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Therapeutic antibodies elicited by immunization against TNF-α

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.

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Figure 1: Immunization with modified mTNF-α molecules elicits autoantibodies cross-reactive with native mTNF-α.
Figure 2: The anti–mTNF-α fine specificity and neutralizing ability of antisera raised by immunization with modified mTNF-α molecules.
Figure 3: Immunization with modified mTNF-α molecules reduces experimental cachexia in mice.
Figure 4: Immunization with mTNF-α ameliorates the symptoms of CIA.

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Acknowledgements

We wish to thank the technicians at M&E Biotech for excellent assistance and Dr. Anand Gautam and Dr. Gunilla Karlsson for useful comments on the manuscript. I.D. was supported by a grant from The Danish Natural Science Research Council, and M.F. and D.M.B. were supported by the Arthritis Research Campaign, UK.

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Correspondence to Søren Mouritsen.

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Dalum, I., Butler, D., Jensen, M. et al. Therapeutic antibodies elicited by immunization against TNF-α. Nat Biotechnol 17, 666–669 (1999). https://doi.org/10.1038/10878

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