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

Laura Ciapponi, Domenico Maione, Ariane Scoumanne, Patrizia Costa, Morten Bagge Hansen, Morten Svenson, Klaus Bendtzen, Tonino Alonzi, Giacomo Paonessa, Riccardo Cortese, Gennaro Ciliberto, Rocco Savino

Research output: Contribution to journalArticlepeer-review

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 (hIL-6), we show that injection of the hIL-6 receptor antagonist Sant1 (an IL-6 valiant with seven amino-acid substitutions) induces a strong anti-hIL-6 antibody response. The elicited antibodies bind circulating hIL-6 with very high affinity, totally masking it, and neutralize hIL-6 bioactivity both in vitro and in vivo.

Original languageEnglish
Pages (from-to)997-1001
Number of pages5
JournalNature Biotechnology
Volume15
Issue number10
Publication statusPublished - Oct 1997

Keywords

  • Autoantibody
  • Autoimmunity
  • Cytokine
  • Receptor antagonist

ASJC Scopus subject areas

  • Microbiology

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