C20 blocks human IL-6 trans-signalling while leaving classic signalling intact.
LONDON, Oct. 15, 2026 (GLOBE NEWSWIRE) -- Mab Designs Ltd today announced the publication of a peer-reviewed study of C20, its anti-interleukin-6 trans-signalling antibody, in Communications Biology, a Nature Portfolio journal.
The paper, "Selective inhibition of IL-6 trans-signalling reveals distinct mechanisms of human classic and trans-signalling receptor-complex formation" (DOI 10.1038/s42003-026-11014-0), reports that C20 blocks human IL-6 trans-signalling while leaving classic IL-6 signalling functionally intact. The work was led by a group at Otto von Guericke University Magdeburg with Mab Designs scientists among the co-authors.
"IL-6 has been a validated target for two decades, but only more recently has the field focused on what the two pathways actually do," said Dr Andrew Clark, co-founder and Managing Director of Mab Designs. "Classic signalling through the membrane-bound receptor underwrites host defence, the hepatic acute-phase response and tissue repair. Trans-signalling through the shed receptor carries inflammation into tissues that would otherwise not respond to IL-6 at all, and it is the arm implicated in a broad range of inflammatory conditions. Every approved antibody in the class blocks both."
C20 binds human IL-6R with picomolar affinity, and leaves IL-11 signalling unaffected. Because it is directed at IL-6R itself rather than at gp130 - the signalling subunit shared across the IL-6 cytokine family - selectivity for IL-6 is intrinsic. C20 binds the soluble and the membrane-bound receptor with comparable affinity yet inhibits only trans-signalling.
Epitope mapping localised a conformational epitope to domain D2 of human IL-6R, distinct from the IL-6 binding site; the authors conclude that C20 most likely blocks binding site IIIb, the contact between IL-6R and gp130. That contact appears dispensable for classic signalling but required for trans-signalling - evidence that the two modes assemble structurally distinct receptor complexes in humans.
"The property we find most interesting is that C20's selectivity is not a binding property," Dr Clark added. "It recognises both forms of the receptor equally well and still blocks only one of them. Selectivity is being exercised at the level of receptor complex assembly rather than target recognition."
The study was carried out under an institutional research agreement between Mab Designs and Otto von Guericke University. Mab Designs had no role in study design, data collection and analysis, or publication decisions. The paper is open access and available at doi.org/10.1038/s42003-026-11014-0.
About Mab Designs Ltd
Mab Designs Ltd, 20 Balderton Street, 6th Floor north, London W1K 6TL. Founded in 2011, Mab Designs use subtractive immunisation protocols to create antibodies against 'difficult' targets. Privately held. www.mabdesigns.co.uk
About C20
C20 is an anti-IL-6R antibody that blocks IL-6 trans-signalling - IC50 3.5 nM as an IgG1, 3.2 nM as a Fab - while leaving classic signalling unaffected at the same concentrations and above. In human liver cells the Fab left the acute-phase response intact; in endothelial cells C20 abolished trans-signalling-driven CCL2 and VEGF expression and returned tube formation to baseline. It binds human IL-6R with picomolar affinity and has no effect on IL-11 signalling: because C20 is directed at IL-6R rather than gp130, the subunit shared across the IL-6 cytokine family, its selectivity is intrinsic.
Contact Dr Andrew Clark, co-founder and CEO, Mab Designs Ltd Tel: +447771641570 andy@mabdesigns.co.uk
