IL-10 is a central anti-inflammatory cytokine that can modulate many pro-inflammatory signals, but clinical application has been limited by dose-limiting systemic side effects. This led to the development of a new chimaera of human IL-10 termed AMT-101.
In mice, the oral gavage of AMT-101 blocked histological changes of colonic tissue associated with oxazolone-induced colitis [1]. AMT-101 curbed increases in serum levels of pro-inflammatory cytokines IL-1β, IL-6, and IL-17A, as well as IL-10 (see Figure). Cynomolgus monkeys dosed orally with AMT-101 showed much lower serum levels than after intravenous injection of AMT-101 [1]. First author Dr Randall Mrsny (Applied Molecular Transport, San Francisco, USA) said these studies provide strong evidence that AMT-101 can effectively reach the intestinal lamina propria to deliver biologically active IL-10 following transcytosis across the intestinal epithelium. The gut-selective nature of the responses suggests AMT-101 may avoid the systemic toxicity of IL-10.
Figure. Serum levels of IL-1β, IL-6, IL-17A, and IL-10 in naïve and in vehicle- and AMT-101-treated mice [1]

Dr Mrsny proposed that AMT-101 has potential as stand-alone as well as combination therapy. A phase 1a study of AMT-101 in healthy subjects has been completed; it is currently being evaluated in a phase 1b trial in patients with active ulcerative colitis. Dr Mrsny stressed that the use of AMT-101 needs not be limited to delivering IL-10: “It is capable of carrying any biological currently in the clinic”.
- Mrsny R, et al. ECCO-IBD 2020, OP39.
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Table of Contents: ECCO 2020
Featured articles
Gut Microbiome as Treatment Target
Response to faecal microbiota transplantation in UC
Bioactives produced by gut bacteria to modulate immune response
Big Data Analysis
Multi-omics help describe CD phenotypes
The positive impact of genetic data on drug development
Experimental Therapies: Study Results
AMT-101: an oral human IL-10 fusion protein
Phase 2 results of first-in-class TL1A inhibitor
Open-label extension study of risankizumab: final results
Clinical remission after dose escalation of upadacitinib
Short- and Long-Term Treatment Results
Infliximab discontinuation increases relapse risk
Tofacitinib ‘real-world’ effectiveness in active UC
Subcutaneous ustekinumab as maintenance therapy in UC
Subcutaneous vedolizumab maintenance therapy in CD
Vedolizumab treatment persistence and safety
Specific Therapeutic Strategies
Impact of strategies on intestinal resection rate
Early ileocaecal resection in CD patients failing conventional treatment
Biologics before surgery in IBD do not elevate infection risk
Top-down infliximab superior to step-up in children with CD
High versus standard adalimumab in active UC
Head-to-Head Comparison of Treatments
Vedolizumab and anti-TNF therapies: a real-world comparison
Cancer Risk
Increased risk of small bowel cancer in IBD
Increased incidence of colorectal cancer and death in CD
Risk of rectal, anal cancer increased in perianal CD
Glyco-fingerprint as risk factor of UC-associated cancer
Miscellaneous Topics
Resolution of mucosal inflammation has dramatic effect
PICaSSO validated in real-life study
Re-inducing inflammation in organoids from UC patients
Role of immune cells in intestinal fibrosis
Association between meat consumption and IBD risk
CD exclusion diet corrects dysbiosis
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