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A Novel Humanized Anti-Interleukin-6 Antibody HZ0408b With Anti-Rheumatoid Arthritis Therapeutic Potential
Liu, Xiaolei Li, Li Wang, Qian Jiang, Fengchao Zhang, Pei Guo, Fei Liu, Hongjun
Liu, Xiaolei
Li, Li
Wang, Qian
Jiang, Fengchao
Zhang, Pei
Guo, Fei
Liu, Hongjun
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2022-01-19
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https://doi.org/10.3389/fimmu.2021.816646
Abstract
Interleukin-6 (IL-6), a pleiotropic cytokine that regulates immune responses and inflammatory reactions, plays a pivotal role in the development of rheumatoid arthritis (RA). Blockade of IL-6 signaling with the monoclonal antibody (mAb) represents an important advancement in RA treatment. Although two IL-6 receptor antibodies are already available in the clinic, there is no mAb specifically targeting the human IL-6 to block IL-6 signaling for RA treatment. In this study, we have developed a novel humanized anti-IL-6 mAb HZ-0408b with potent binding and neutralizing activity to human IL-6. We demonstrated that HZ-0408b has a high species specificity and low cross-reactivity. Moreover, HZ-0408b showed a more potent inhibitory effect on IL-6 signaling than Siltuximab, an FDA-approved anti-IL-6 chimeric mAb. HZ-0408b is comparable to Olokizumab, a humanized mAb against IL-6 that is already in phase III studies. We observed that HZ-0408b is well tolerated at doses that can achieve therapeutic serum levels in cynomolgus monkey. Most importantly, we proved that HZ-0408b treatment significantly ameliorated joint swelling after the onset of arthritis and dramatically reduced plasma C-reactive protein (CRP) levels in a monkey collagen-induced arthritis (CIA) model. Collectively, our findings using non-human primates indicate that humanized anti-IL-6 mAb HZ-0408b has excellent safety and efficacy profiles for RA therapy.
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Liu X, Li L, Wang Q, Jiang F, Zhang P, Guo F, Liu H and Huang J (2022) A Novel Humanized Anti-Interleukin-6 Antibody HZ0408b With Anti-Rheumatoid Arthritis Therapeutic Potential. Front. Immunol. 12:816646. doi: 10.3389/fimmu.2021.816646
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Frontiers in Immunology, Vol. 12
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