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dc.creatorLiu, Xiaolei
dc.creatorLi, Li
dc.creatorWang, Qian
dc.creatorJiang, Fengchao
dc.creatorZhang, Pei
dc.creatorGuo, Fei
dc.creatorLiu, Hongjun
dc.creatorhuang, Jian
dc.date.accessioned2022-04-29T19:21:41Z
dc.date.available2022-04-29T19:21:41Z
dc.date.issued2022-01-19
dc.identifier.citationLiu 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
dc.identifier.issn1664-3224
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/7594
dc.identifier.urihttp://hdl.handle.net/20.500.12613/7616
dc.description.abstractInterleukin-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.
dc.format.extent10 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartFrontiers in Immunology, Vol. 12
dc.relation.isreferencedbyFrontiers Media
dc.rightsAttribution CC BY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectMonoclonal antibody
dc.subjectRheumatoid arthritis
dc.subjectIL-6
dc.subjectAutoimmune disease
dc.subjectCollagen-induced arthritis (CIA) model
dc.titleA Novel Humanized Anti-Interleukin-6 Antibody HZ0408b With Anti-Rheumatoid Arthritis Therapeutic Potential
dc.typeText
dc.type.genreJournal article
dc.contributor.groupCenter for Metabolic Disease Research (Temple University)
dc.relation.doihttps://doi.org/10.3389/fimmu.2021.816646
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeLewis Katz School of Medicine
dc.creator.orcidHuang|0000-0002-1649-0038
dc.temple.creatorHuang, Jian
refterms.dateFOA2022-04-29T19:21:41Z


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