Related Experiment Video
Updated: Nov 15, 2025

Adoptive Immunotherapy of iNKT Cells in Glucose-6-Phosphate Isomerase G6PI-Induced RA Mice
Published on: January 31, 2020
Therapeutic Interleukin-6 Trans-signaling Inhibition by Olamkicept (sgp130Fc) in Patients With Active Inflammatory
Stefan Schreiber1, Konrad Aden1, Joana P Bernardes2
1Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany; Institute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Background & Aims:
A large unmet therapeutic need exists in inflammatory bowel disease (IBD). Inhibition of interleukin (IL)-6 appears to be effective, but the therapeutic benefit of a complete IL6/IL6 receptor (IL6R) blockade is limited by profound immunosuppression. Evidence has emerged that chronic proinflammatory activity of IL6 is mainly mediated by trans-signaling via a complex of IL6 bound to soluble IL6R engaging the gp130 co-receptor without the need for membrane-bound IL6R. We have developed a decoy protein, sgp130Fc, that exclusively blocks IL6 proinflammatory trans-signaling and has shown efficacy in preclinical models of IBD, without signs of immunosuppression.
Methods:
We present a 12-week, open-label, prospective phase 2a trial (FUTURE) in 16 patients with active IBD treated with the trans-signaling inhibitor olamkicept (sgp130Fc) to assess the molecular mechanisms, safety, and effectiveness of IL6 trans-signaling blockade in vivo. We performed in-depth molecular profiling at various timepoints before and after therapy induction to identify the mechanism of action of olamkicept.
Results:
Olamkicept was well tolerated and induced clinical response in 44% and clinical remission in 19% of patients. Clinical effectiveness coincided with target inhibition (reduction of phosphorylated STAT3) and marked transcriptional changes in the inflamed mucosa. An olamkicept-specific transcriptional signature, distinguishable from remission signatures of anti-tumor necrosis factor (infliximab) or anti-integrin (vedolizumab) therapies was identified.
Conclusions:
Our data suggest that blockade of IL6 trans-signaling holds great promise for the therapy of IBD and should undergo full clinical development as a new immunoregulatory therapy for IBD. (EudraCT no., Nu 2016-000205-36).
More Related Videos
05:41Therapeutic Evaluation of Fecal Microbiota Transplantation in an Interleukin 10-Deficient Mouse Model
Published on: April 6, 2022
09:01Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice
Published on: March 10, 2015
Related Concept Videos
Inflammatory Bowel Disease IV: Pharmacological Management
Pharmacologic...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
The JAK-STAT Signaling Pathway