Matches in SemOpenAlex for { <https://semopenalex.org/work/W4376135313> ?p ?o ?g. }
Showing items 1 to 96 of
96
with 100 items per page.
- W4376135313 endingPage "126" @default.
- W4376135313 startingPage "119" @default.
- W4376135313 abstract "Abstract Dysregulated elevation of interleukin-6 (IL-6) signaling is implicated in the pathogenesis of multiple pathophysiological states, and the functional neutralization of the IL-6 pathway with monoclonal antibodies has been proven an effective therapeutic method in treating various diseases with abnormally enhanced IL-6 signaling, and its clinical indications are expanding. Here, we report that by using the conventional hybridoma technology and humanization mutation method, we develop a novel humanized anti-IL-6 receptor (IL-6R) antibody—namely, HZ0412a. In our study, we found that HZ0412a exhibits higher binding affinity to soluble recombinant human IL-6R than tocilizumab. Importantly, in contrast to tocilizumab—a humanized anti-IL-6R antibody approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis and Castleman’s disease—HZ0412a does not significantly affect the binding of IL-6 to IL-6R. Further analysis revealed that HZ0412a prevents IL-6R from binding to gp130 in vitro, while tocilizumab has a minimal effect under the same condition. Using various cell-based assays, we demonstrate that HZ0412a is noninferior to tocilizumab in inhibiting IL-6 signaling. Finally, we showed that HZ0412a is well tolerated in cynomolgus monkeys after a single subcutaneous injection at a dose of 1 or 5 mg/kg. Taken together, our results indicated that HZ0412a targets an epitope on human IL-6R that is different from that of tocilizumab, and the epitope region is essential for the interaction between IL-6R and gp130. This distinctive mode of action plus its high affinity to IL-6R led to the high potency of HZ0412a in suppressing in vitro IL-6 signaling." @default.
- W4376135313 created "2023-05-12" @default.
- W4376135313 creator A5002752646 @default.
- W4376135313 creator A5018764399 @default.
- W4376135313 creator A5023371990 @default.
- W4376135313 creator A5025561894 @default.
- W4376135313 creator A5027475930 @default.
- W4376135313 creator A5027896601 @default.
- W4376135313 creator A5052676364 @default.
- W4376135313 creator A5057147306 @default.
- W4376135313 creator A5077385497 @default.
- W4376135313 creator A5091923868 @default.
- W4376135313 date "2023-04-01" @default.
- W4376135313 modified "2023-10-18" @default.
- W4376135313 title "Characterization of HZ0412a, a novel potent humanized anti-IL-6 receptor antibody that blocks IL-6R binding to gp130" @default.
- W4376135313 cites W2001941062 @default.
- W4376135313 cites W2013714853 @default.
- W4376135313 cites W2074443373 @default.
- W4376135313 cites W2078831149 @default.
- W4376135313 cites W2153853625 @default.
- W4376135313 cites W2291386925 @default.
- W4376135313 cites W2557016092 @default.
- W4376135313 cites W2565354684 @default.
- W4376135313 cites W2894776217 @default.
- W4376135313 cites W2938774134 @default.
- W4376135313 cites W2998780539 @default.
- W4376135313 cites W3017957088 @default.
- W4376135313 cites W3032543466 @default.
- W4376135313 cites W3129717864 @default.
- W4376135313 cites W4206569802 @default.
- W4376135313 cites W4234268725 @default.
- W4376135313 cites W4293105517 @default.
- W4376135313 cites W91258909 @default.
- W4376135313 doi "https://doi.org/10.1093/abt/tbad008" @default.
- W4376135313 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37324549" @default.
- W4376135313 hasPublicationYear "2023" @default.
- W4376135313 type Work @default.
- W4376135313 citedByCount "0" @default.
- W4376135313 crossrefType "journal-article" @default.
- W4376135313 hasAuthorship W4376135313A5002752646 @default.
- W4376135313 hasAuthorship W4376135313A5018764399 @default.
- W4376135313 hasAuthorship W4376135313A5023371990 @default.
- W4376135313 hasAuthorship W4376135313A5025561894 @default.
- W4376135313 hasAuthorship W4376135313A5027475930 @default.
- W4376135313 hasAuthorship W4376135313A5027896601 @default.
- W4376135313 hasAuthorship W4376135313A5052676364 @default.
- W4376135313 hasAuthorship W4376135313A5057147306 @default.
- W4376135313 hasAuthorship W4376135313A5077385497 @default.
- W4376135313 hasAuthorship W4376135313A5091923868 @default.
- W4376135313 hasBestOaLocation W43761353131 @default.
- W4376135313 hasConcept C11988809 @default.
- W4376135313 hasConcept C126037660 @default.
- W4376135313 hasConcept C159654299 @default.
- W4376135313 hasConcept C195616568 @default.
- W4376135313 hasConcept C203014093 @default.
- W4376135313 hasConcept C2777092746 @default.
- W4376135313 hasConcept C2777178219 @default.
- W4376135313 hasConcept C2777575956 @default.
- W4376135313 hasConcept C2778690821 @default.
- W4376135313 hasConcept C542903549 @default.
- W4376135313 hasConcept C71924100 @default.
- W4376135313 hasConcept C98274493 @default.
- W4376135313 hasConceptScore W4376135313C11988809 @default.
- W4376135313 hasConceptScore W4376135313C126037660 @default.
- W4376135313 hasConceptScore W4376135313C159654299 @default.
- W4376135313 hasConceptScore W4376135313C195616568 @default.
- W4376135313 hasConceptScore W4376135313C203014093 @default.
- W4376135313 hasConceptScore W4376135313C2777092746 @default.
- W4376135313 hasConceptScore W4376135313C2777178219 @default.
- W4376135313 hasConceptScore W4376135313C2777575956 @default.
- W4376135313 hasConceptScore W4376135313C2778690821 @default.
- W4376135313 hasConceptScore W4376135313C542903549 @default.
- W4376135313 hasConceptScore W4376135313C71924100 @default.
- W4376135313 hasConceptScore W4376135313C98274493 @default.
- W4376135313 hasIssue "2" @default.
- W4376135313 hasLocation W43761353131 @default.
- W4376135313 hasLocation W43761353132 @default.
- W4376135313 hasLocation W43761353133 @default.
- W4376135313 hasOpenAccess W4376135313 @default.
- W4376135313 hasPrimaryLocation W43761353131 @default.
- W4376135313 hasRelatedWork W1508108563 @default.
- W4376135313 hasRelatedWork W195682249 @default.
- W4376135313 hasRelatedWork W1981898410 @default.
- W4376135313 hasRelatedWork W2059923545 @default.
- W4376135313 hasRelatedWork W2063604066 @default.
- W4376135313 hasRelatedWork W2091594406 @default.
- W4376135313 hasRelatedWork W2329860994 @default.
- W4376135313 hasRelatedWork W3105097885 @default.
- W4376135313 hasRelatedWork W3134848079 @default.
- W4376135313 hasRelatedWork W4252441337 @default.
- W4376135313 hasVolume "6" @default.
- W4376135313 isParatext "false" @default.
- W4376135313 isRetracted "false" @default.
- W4376135313 workType "article" @default.