AZ17: a new bispecific drug targeting IL-6 and IL-23 with potential clinical use—improves psoriasis in a human xenograft transplantation model

Karin Stenderup et. al., 28(10):467-480, Protein Engineering, Design and Selection, 2015

Psoriasis is a multifactorial disease in which interleukin (IL)-6 and IL-23 are important disease mediators because they facilitate development of Th17 cells. The group aimed to develop clinically relevant bispecific antibodies targeting IL-6 and IL-23 exhibiting high affinity, high stability and the ability to be produced in high yield. Thus, the bispecific drug molecule AZ17 has the potential to alleviate psoriasis. Stability of the drug and its long residence time in vivo was achieved by introducing flexible poly-ethylene glycol molecule into the structure. ForteBio Pioneer technology (SensiQ Pioneer system) was applied to measure affinity of AZ17 towards IL-6 andIL-23. Kinetic parameters were measured using a carboxylated COOH1 sensor. The sample running buffer was Hepes-buffered saline (HBS), containing 10 mM Hepes, 150 mM NaCl (pH 7.4), 0.001% Tween 20 and 3 mM EDTA. The assay temperature was maintained at 25°C with an analyte flow rate of 50 μl/min, including a 2 min association phase and a 10–30 min dissociation phase. Binding affinity studies resulted in determination of KD of 215 pM for IL-6 and KD of 92 pM for IL-23. Additionally, the kinetic parameters of anti-IL-6-scFv were measured and obtained KD = 98 pM, demonstrated a reduction in the IL-6 affinity in AZ17.

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