A novel antibody has shown promise for conditions such as rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease (IBD), researchers reported today.
The Ab-IPL-IL-17™ antibody targets a specific section of both interleukin-17A and F, which play a central role in sustaining inflammation during onset and progression of autoimmune diseases.
Research published last night in Annals of Rheumatic Diseases identifies the sequence and reports the results of animal, cell and tissue studies that show how effective Ab-IPL-IL-17™ could be for people with RA and IBD.
Authors Dr Asif Iqbal from the University of Birmingham, UK, and Professor Francesco Maione, head of ImmunoPharma Lab from the University of Naples Federico II, Italy, say Ab-IPL-IL-17™ displays potent anti-inflammatory activity in tissue and animal studies, adding that it maintains this activity without triggering unwanted ‘off target’ effects, which are sometimes seen in less specific antibody therapies.
They add that Ab-IPL-IL-17™ also reduces the pathological symptoms of arthritis and inflammatory bowel disease and is as effective as the current gold-standard treatment for RA at halting disease progression and triggering resolution.
IL-17A and IL-17F stimulate molecular signals that initiate inflammation and cause tissue damage and have been linked to numerous immune-mediated inflammatory diseases (IMIDs) and the researchers designed a series of peptides based on IL-17A/F and tested their ability to mimic the actions of the full proteins in cell culture.
They found a sequence, which they named nIL-17™, that was 20 amino acids long and was shown to be responsible for IL-17’s biological activity in both mice and humans.
They went on to show on an atomic level, how the sequence ‘docks’ onto receptors that are known to trigger an inflammatory response and that it is this short sequence that is a potent activator of the inflammatory response.
The results were confirmed in animal models, which showed the nIL-17™ represents the most biologically active sequence of IL-17.
Mouse studies evaluating the activity of Ab-IPL-IL-17™ against secukinumab, ixekizumab and bimekizumab, which are anti-IL-17 therapies, showed Ab-IPL-IL-17™ does not trigger unwanted immune responses, reduce the numbers of platelets, or increase the numbers of lymphocytes in the blood.
Further studies in mouse models of arthritis showed therapeutic administration of Ab-IPL-IL-17™ is as effective at halting disease progression and triggering resolution as the gold-standard current treatment for RA, infliximab.
In proof-of-concept studies, which tested the response of tissues donated by patients with RA and IBD to Ab-IPL-IL-17™, they found it reduce the pathological symptoms of disease.
New biologic (Ab-IPL-IL17™) for IL-17-mediated diseases: Identification of the bioactive sequence (nIL-17™) for IL-17A/F function. Annals of Rheumatic Diseases 14 August 2023; doi: 10.1136/ard-2023-224479
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