A Novel Humanized Anti-Interleukin-6 Antibody HZ0408b With Anti-Rheumatoid Arthritis Therapeutic Potential
dc.creator | Liu, Xiaolei | |
dc.creator | Li, Li | |
dc.creator | Wang, Qian | |
dc.creator | Jiang, Fengchao | |
dc.creator | Zhang, Pei | |
dc.creator | Guo, Fei | |
dc.creator | Liu, Hongjun | |
dc.creator | huang, Jian | |
dc.date.accessioned | 2022-04-29T19:21:41Z | |
dc.date.available | 2022-04-29T19:21:41Z | |
dc.date.issued | 2022-01-19 | |
dc.identifier.citation | 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 | |
dc.identifier.issn | 1664-3224 | |
dc.identifier.doi | http://dx.doi.org/10.34944/dspace/7594 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12613/7616 | |
dc.description.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. | |
dc.format.extent | 10 pages | |
dc.language | English | |
dc.language.iso | eng | |
dc.relation.ispartof | Faculty/ Researcher Works | |
dc.relation.haspart | Frontiers in Immunology, Vol. 12 | |
dc.relation.isreferencedby | Frontiers Media | |
dc.rights | Attribution CC BY | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Monoclonal antibody | |
dc.subject | Rheumatoid arthritis | |
dc.subject | IL-6 | |
dc.subject | Autoimmune disease | |
dc.subject | Collagen-induced arthritis (CIA) model | |
dc.title | A Novel Humanized Anti-Interleukin-6 Antibody HZ0408b With Anti-Rheumatoid Arthritis Therapeutic Potential | |
dc.type | Text | |
dc.type.genre | Journal article | |
dc.contributor.group | Center for Metabolic Disease Research (Temple University) | |
dc.relation.doi | https://doi.org/10.3389/fimmu.2021.816646 | |
dc.ada.note | For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu | |
dc.description.schoolcollege | Lewis Katz School of Medicine | |
dc.creator.orcid | Huang|0000-0002-1649-0038 | |
dc.temple.creator | Huang, Jian | |
refterms.dateFOA | 2022-04-29T19:21:41Z |