Development of Bispecific Antibody Targeting Human IL-17A and IL-6

Area of Science:

• Biotechnology
• Immunology
• Drug Discovery

Background:

• Monospecific antibodies have limitations in treating complex inflammatory diseases.
• Multispecific therapeutics offer enhanced efficacy and reduced side effects by targeting multiple antigens.
• Interleukin-6 (IL-6) and Interleukin-17A (IL-17A) are key cytokines in autoimmune and inflammatory conditions.

Purpose of the Study:

• To identify and characterize bispecific, VHH-based antibodies targeting both IL-6 and IL-17A.
• To evaluate the binding affinity, functional activity, and biophysical properties of these bispecific antibodies.

Main Methods:

• Phage display screening of llama-derived VHH libraries against human IL-6 and IL-17A.
• Bio-Layer Interferometry (BLI) for binding affinity assessment.
• Reporter cell lines for functional activity evaluation.
• Uncle screening platform and LabChip capillary electrophoresis for biophysical and quality assessments.

Main Results:

• Identification of high-affinity VHH binders for both IL-6 and IL-17A.
• Successful assembly of bispecific antibody formats.
• Demonstrated simultaneous inhibition of IL-6 and IL-17A signaling pathways in functional assays.
• Selected bispecific antibodies showed good stability and purity profiles.

Conclusions:

• Feasibility of generating stable, functional bispecific VHH antibodies targeting IL-6 and IL-17A.
• These bispecific antibodies hold potential as therapeutic agents for autoimmune and chronic inflammatory diseases.
• Simultaneous modulation of multiple cytokine pathways offers a promising therapeutic strategy.