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Induction of interleukin-6 (IL-6) autoantibodies through vaccination with an engineered IL-6 receptor antagonist

Nature Biotechnology volume 15, pages 997–1001 (1997)Cite this article

Abstract

Neutralization of cytokine activity by monoclonal antibodies or receptor antagonists is beneficial in the treatment of immune and neoplastic diseases, but the necessity for continuous parenteral delivery of these anticytokine agents poses considerable practical limitations. A viable alternative is to induce a neutralizing antibody response. Using transgenic mice with high circulating levels of human interleukin-6 (hlL-6), we show that injection of the hlL-6 receptor antagonist Santi (an IL-6 variant with seven amino-acid substitutions) induces a strong anti-hlL-6 antibody response. The elicited antibodies bind circulating hlL-6 with very high affinity, totally masking it, and neutralize hlL-6 bioactivity both in vitro and in vivo

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Author information

Author notes

  1. Laura Ciapponi and Domenico Maione: These two authors have contributed equally to the work.

  2. Gennaro Ciliberto: e-mail: ciliberto@irbm.it.

Authors and Affiliations

  1. I.R.B.M.P.Angeletti, Via Pontina km 30, 600, 00040, Pomezia, Rome, Italy

    Ariane Scoumanne, Patrizia Costa, Tonino Alonzi, Giacomo Paonessa, Riccardo Cortese & Rocco Savino

  2. Department of Clinical Immunology, Rigshospitalet, University Hospital, Copenhagen, Denmark

    Morten Bagge Hansen

  3. Institute for Inflammation Research, Rigshospitalet, University Hospital, Copenhagen, Denmark

    Morten Bagge Hansen, Morten Svenson & Klaus Bendtzen

Authors
  1. Laura Ciapponi
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  2. Domenico Maione
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  3. Ariane Scoumanne
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  4. Patrizia Costa
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  5. Morten Bagge Hansen
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  6. Morten Svenson
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  7. Klaus Bendtzen
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  8. Tonino Alonzi
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  9. Giacomo Paonessa
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  11. Gennaro Ciliberto
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  12. Rocco Savino
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Ciapponi, L., Maione, D., Scoumanne, A. et al. Induction of interleukin-6 (IL-6) autoantibodies through vaccination with an engineered IL-6 receptor antagonist. Nat Biotechnol 15, 997–1001 (1997). https://doi.org/10.1038/nbt1097-997

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  • DOI: https://doi.org/10.1038/nbt1097-997

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