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

Area of Science:

• Immunology
• Biotechnology
• Pharmacology

Background:

• Interleukin (IL)-17 cytokines are central to inflammation in immune-mediated inflammatory diseases (IMIDs).
• Current therapies targeting IL-17s have limitations in efficacy and tolerability for certain patients and conditions.
• There is a critical need for improved antibody treatments targeting IL-17A, IL-17F, and their heterodimers.

Purpose of the Study:

• To develop a novel monoclonal antibody (Ab-IPL-IL-17) for neutralizing IL-17A/F activity.
• To assess the efficacy and safety profile of Ab-IPL-IL-17 compared to existing treatments.
• To evaluate the therapeutic potential of Ab-IPL-IL-17 in preclinical models and patient samples.

Main Methods:

• Identification of a bioactive peptide (nIL-17) mimicking IL-17A/F.
• Generation and characterization of the neutralizing monoclonal antibody Ab-IPL-IL-17.
• Comparative analysis of Ab-IPL-IL-17 against secukinumab in murine models of arthritis and in patient-derived samples from rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) cohorts.

Main Results:

• Ab-IPL-IL-17 effectively neutralized the pro-inflammatory and pro-migratory effects of nIL-17 and IL-17A/F.
• The novel antibody demonstrated fewer off-target effects compared to secukinumab.
• Ab-IPL-IL-17 significantly reduced clinical signs of arthritis in preclinical models and normalized IL-17 levels in IBD patient serum.

Conclusions:

• Preclinical and in vitro data strongly support the high efficacy and therapeutic potency of Ab-IPL-IL-17.
• Ab-IPL-IL-17 presents a promising therapeutic candidate for IMIDs.
• Further clinical evaluation in patients with IMIDs is warranted.