Chemically Modified Interleukin-6 Aptamer Inhibits Development of Collagen-Induced Arthritis in Cynomolgus Monkeys

Nucleic Acid Ther. 2016 Feb;26(1):10-9. doi: 10.1089/nat.2015.0567. Epub 2015 Nov 18.


Interleukin-6 (IL-6) is a potent mediator of inflammatory and immune responses, and a validated target for therapeutic intervention of inflammatory diseases. Previous studies have shown that SL1026, a slow off-rate modified aptamer (SOMAmer) antagonist of IL-6, neutralizes IL-6 signaling in vitro. In the present study, we show that SL1026 delays the onset and reduces the severity of rheumatoid symptoms in a collagen-induced arthritis model in cynomolgus monkeys. SL1026 (1 and 10 mg/kg), administered q.i.d., delayed the progression of arthritis and the concomitant increase in serum IL-6 levels compared to the untreated control group. Furthermore, SL1026 inhibited IL-6-induced STAT3 phosphorylation ex vivo in T lymphocytes from human blood and IL-6-induced C-reactive protein and serum amyloid A production in human primary hepatocytes. Importantly, SOMAmer treatment did not elicit an immune response, as evidenced by the absence of anti-SOMAmer antibodies in plasma of treated monkeys. These results demonstrate that SOMAmer antagonists of IL-6 may be attractive agents for the treatment of IL-6-mediated diseases, including rheumatoid arthritis.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aptamers, Peptide / chemistry*
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / prevention & control*
  • Cells, Cultured
  • Collagen / adverse effects*
  • Female
  • Humans
  • Interleukin-6 / blood*
  • Interleukin-6 / chemistry
  • Macaca fascicularis
  • Molecular Sequence Data
  • Phosphorylation
  • STAT3 Transcription Factor / metabolism
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / metabolism


  • Aptamers, Peptide
  • Interleukin-6
  • STAT3 Transcription Factor
  • Collagen