New biologic (Ab-IPL-IL-17) for IL-17-mediated diseases: identification of the bioactive sequence (nIL-17) for IL-17A/F function.

Autor:	Saviano A; ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Napoli, Italy., Manosour AA; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia., Raucci F; ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Napoli, Italy., Merlino F; Department of Pharmacy, University of Naples Federico II, Napoli, Italy., Marigliano N; ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Napoli, Italy., Schettino A; ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Napoli, Italy., Wahid M; Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Begum J; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Filer A; Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Manning JE; Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Casillo GM; Department of Pharmacy, University of Naples Federico II, Napoli, Italy., Piccolo M; BioChemLab, Department of Pharmacy, University of Naples Federico II, Napoli, Italy., Ferraro MG; BioChemLab, Department of Pharmacy, University of Naples Federico II, Napoli, Italy., Marzano S; Department of Pharmacy, University of Naples Federico II, Napoli, Italy., Russomanno P; Department of Pharmacy, University of Naples Federico II, Napoli, Italy., Bellavita R; Department of Pharmacy, University of Naples Federico II, Napoli, Italy., Irace C; BioChemLab, Department of Pharmacy, University of Naples Federico II, Napoli, Italy., Amato J; Department of Pharmacy, University of Naples Federico II, Napoli, Italy., Alfaifi M; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia., Rimmer P; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.; Department of Gastroenterology, Queen Elizabeth Hospital Birmingham, Birmingham, UK., Iqbal T; Department of Gastroenterology, Queen Elizabeth Hospital Birmingham, Birmingham, UK.; Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Pieretti S; Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Roma, Italy., Vellecco V; Department of Pharmacy, University of Naples Federico II, Napoli, Italy., Caso F; Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy., Costa L; Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy., Giacomelli R; Fondazione Policlinico Universitario, and Research Unit of Immuno-Rheumatology, Department of Medicine and Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Roma, Italy, and Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy, Roma, Italy., Scarpa R; Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy., Cirino G; Department of Pharmacy, University of Naples Federico II, Napoli, Italy., Bucci M; Department of Pharmacy, University of Naples Federico II, Napoli, Italy., McGettrick HM; Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Grieco P; Department of Pharmacy, University of Naples Federico II, Napoli, Italy., Iqbal AJ; Department of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK francesco.maione@unina.it a.j.iqbal@bham.ac.uk., Maione F; ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Napoli, Italy francesco.maione@unina.it a.j.iqbal@bham.ac.uk.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2023 Nov; Vol. 82 (11), pp. 1415-1428. Date of Electronic Publication: 2023 Aug 14.
DOI:	10.1136/ard-2023-224479
Abstrakt:	Objectives: Interleukin (IL) 17s cytokines are key drivers of inflammation that are functionally dysregulated in several human immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis (RA), psoriasis and inflammatory bowel disease (IBD). Targeting these cytokines has some therapeutic benefits, but issues associated with low therapeutic efficacy and immunogenicity for subgroups of patients or IMIDs reduce their clinical use. Therefore, there is an urgent need to improve the coverage and efficacy of antibodies targeting IL-17A and/or IL-17F and IL-17A/F heterodimer. Methods and Results: Here, we initially identified a bioactive 20 amino acid IL-17A/F-derived peptide (nIL-17) that mimics the pro-inflammatory actions of the full-length proteins. Subsequently, we generated a novel anti-IL-17 neutralising monoclonal antibody (Ab-IPL-IL-17) capable of effectively reversing the pro-inflammatory, pro-migratory actions of both nIL-17 and IL-17A/F. Importantly, we demonstrated that Ab-IPL-IL-17 has less off-target effects than the current gold-standard biologic, secukinumab. Finally, we compared the therapeutic efficacy of Ab-IPL-IL-17 with reference anti-IL-17 antibodies in preclinical murine models and samples from patients with RA and IBD. We found that Ab-IPL-IL-17 could effectively reduce clinical signs of arthritis and neutralise elevated IL-17 levels in IBD patient serum. Conclusions: Collectively, our preclinical and in vitro clinical evidence indicates high efficacy and therapeutic potency of Ab-IPL-IL-17, supporting the rationale for large-scale clinical evaluation of Ab-IPL-IL-17 in patients with IMIDs. Competing Interests: Competing interests: This article has been conducted and written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors ASaviano, FR, FMerlino, RB, PG, MB, AJI and FMaione hold patents for the diagnostic and therapeutic use of nIL-17 and Ab-IPL-IL-17 (IT patent no.: 102022000016722) in autoimmune disease, chronic inflammatory disease and other diseases in which IL-17 producing cells contribute to pathogenesis. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ on behalf of EULAR.)
Databáze:	MEDLINE
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