Generation and characterization of human B lymphocyte stimulator blocking monoclonal antibody
•A new humanized anti-Blys antibody was developed.•The antibody binds with sub-nanomolar affinity and high specificity.•The antibody significantly inhibited Blys induced B cell proliferation, in vivo. The cytokine, B lymphocyte stimulator (Blys) is essential for activation and proliferation of B cel...
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Veröffentlicht in: | Molecular immunology 2016-09, Vol.77, p.141-147 |
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creator | Zhuang, Weiliang Zhang, Jianjun Pei, Lili Fang, Shuping Liu, Honghao Wang, Ruixue Su, Yunpeng |
description | •A new humanized anti-Blys antibody was developed.•The antibody binds with sub-nanomolar affinity and high specificity.•The antibody significantly inhibited Blys induced B cell proliferation, in vivo.
The cytokine, B lymphocyte stimulator (Blys) is essential for activation and proliferation of B cells and is involved in the pathogenesis of B-cell mediated autoimmune diseases. Based on its essential activity, Blys may be a potential therapeutic target for human autoimmune diseases. In this article, we have described the development of a novel humanized anti-Blys antibody, NMB04, that binds with high affinity and specificity to both soluble and membrane bound Blys. This monoclonal antibody has the potential to block Blys binding to all its three receptors, TACI, BCMA and BR-3. Further in vivo studies revealed that NMB04 possessed more potent inhibitory activity against human Blys as compared to an existing antibody, Belimumab. Therefore, NMB04 may have potential as a therapeutic candidate targeting autoimmune diseases. |
doi_str_mv | 10.1016/j.molimm.2016.08.002 |
format | Article |
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The cytokine, B lymphocyte stimulator (Blys) is essential for activation and proliferation of B cells and is involved in the pathogenesis of B-cell mediated autoimmune diseases. Based on its essential activity, Blys may be a potential therapeutic target for human autoimmune diseases. In this article, we have described the development of a novel humanized anti-Blys antibody, NMB04, that binds with high affinity and specificity to both soluble and membrane bound Blys. This monoclonal antibody has the potential to block Blys binding to all its three receptors, TACI, BCMA and BR-3. Further in vivo studies revealed that NMB04 possessed more potent inhibitory activity against human Blys as compared to an existing antibody, Belimumab. Therefore, NMB04 may have potential as a therapeutic candidate targeting autoimmune diseases.</description><identifier>ISSN: 0161-5890</identifier><identifier>EISSN: 1872-9142</identifier><identifier>DOI: 10.1016/j.molimm.2016.08.002</identifier><identifier>PMID: 27505709</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - pharmacology ; Antibody ; Antibody Affinity - immunology ; Antibody Specificity - immunology ; Autoimmune ; B-Cell Activating Factor - immunology ; B-Lymphocytes - drug effects ; B-Lymphocytes - immunology ; Blys ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Lymphocyte Activation - drug effects ; Lymphocyte Activation - immunology ; Macaca fascicularis ; Male ; Mice ; Mice, Inbred BALB C ; Polymerase Chain Reaction ; SLE</subject><ispartof>Molecular immunology, 2016-09, Vol.77, p.141-147</ispartof><rights>2016 Elsevier Ltd</rights><rights>Copyright © 2016 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c296t-858c5d8c062d74a596ba111e34229f02377e16b61002ebc68016dbd0edc0a493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.molimm.2016.08.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27505709$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhuang, Weiliang</creatorcontrib><creatorcontrib>Zhang, Jianjun</creatorcontrib><creatorcontrib>Pei, Lili</creatorcontrib><creatorcontrib>Fang, Shuping</creatorcontrib><creatorcontrib>Liu, Honghao</creatorcontrib><creatorcontrib>Wang, Ruixue</creatorcontrib><creatorcontrib>Su, Yunpeng</creatorcontrib><title>Generation and characterization of human B lymphocyte stimulator blocking monoclonal antibody</title><title>Molecular immunology</title><addtitle>Mol Immunol</addtitle><description>•A new humanized anti-Blys antibody was developed.•The antibody binds with sub-nanomolar affinity and high specificity.•The antibody significantly inhibited Blys induced B cell proliferation, in vivo.
The cytokine, B lymphocyte stimulator (Blys) is essential for activation and proliferation of B cells and is involved in the pathogenesis of B-cell mediated autoimmune diseases. Based on its essential activity, Blys may be a potential therapeutic target for human autoimmune diseases. In this article, we have described the development of a novel humanized anti-Blys antibody, NMB04, that binds with high affinity and specificity to both soluble and membrane bound Blys. This monoclonal antibody has the potential to block Blys binding to all its three receptors, TACI, BCMA and BR-3. Further in vivo studies revealed that NMB04 possessed more potent inhibitory activity against human Blys as compared to an existing antibody, Belimumab. Therefore, NMB04 may have potential as a therapeutic candidate targeting autoimmune diseases.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibody</subject><subject>Antibody Affinity - immunology</subject><subject>Antibody Specificity - immunology</subject><subject>Autoimmune</subject><subject>B-Cell Activating Factor - immunology</subject><subject>B-Lymphocytes - drug effects</subject><subject>B-Lymphocytes - immunology</subject><subject>Blys</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Humans</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Lymphocyte Activation - immunology</subject><subject>Macaca fascicularis</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Polymerase Chain Reaction</subject><subject>SLE</subject><issn>0161-5890</issn><issn>1872-9142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UE1v1DAQtRAVXVr-AUI5ckkYexPHuSBBBW2lSlx6rSzHnmW9-GOxnUrbX4-rFI6cRjPzPvQeIe8pdBQo_3TofHTW-47VrQPRAbBXZEPFyNqJ9uw12dQHbQcxwTl5m_MBADjw4Q05Z-MAwwjThjxcY8Ckio2hUcE0eq-S0gWTfVqPcdfsF69C87VxJ3_cR30q2ORi_eJUiamZXdS_bPjZ-BiidjEoV5WKnaM5XZKznXIZ373MC3L__dv91U179-P69urLXavZxEsrBqEHIzRwZsZeDROfFaUUtz1j0w7YdhyR8pnTGhFnzUUNZmYDaDSoftpekI-r7DHF3wvmIr3NGp1TAeOSJRWU860YJqjQfoXqFHNOuJPHZL1KJ0lBPvcqD3LtVT73KkHIalppH14cltmj-Uf6W2QFfF4BWGM-Wkwya4tBo7EJdZEm2v87_AHC3Yxo</recordid><startdate>201609</startdate><enddate>201609</enddate><creator>Zhuang, Weiliang</creator><creator>Zhang, Jianjun</creator><creator>Pei, Lili</creator><creator>Fang, Shuping</creator><creator>Liu, Honghao</creator><creator>Wang, Ruixue</creator><creator>Su, Yunpeng</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201609</creationdate><title>Generation and characterization of human B lymphocyte stimulator blocking monoclonal antibody</title><author>Zhuang, Weiliang ; Zhang, Jianjun ; Pei, Lili ; Fang, Shuping ; Liu, Honghao ; Wang, Ruixue ; Su, Yunpeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c296t-858c5d8c062d74a596ba111e34229f02377e16b61002ebc68016dbd0edc0a493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antibody</topic><topic>Antibody Affinity - immunology</topic><topic>Antibody Specificity - immunology</topic><topic>Autoimmune</topic><topic>B-Cell Activating Factor - immunology</topic><topic>B-Lymphocytes - drug effects</topic><topic>B-Lymphocytes - immunology</topic><topic>Blys</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Humans</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Lymphocyte Activation - immunology</topic><topic>Macaca fascicularis</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Polymerase Chain Reaction</topic><topic>SLE</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhuang, Weiliang</creatorcontrib><creatorcontrib>Zhang, Jianjun</creatorcontrib><creatorcontrib>Pei, Lili</creatorcontrib><creatorcontrib>Fang, Shuping</creatorcontrib><creatorcontrib>Liu, Honghao</creatorcontrib><creatorcontrib>Wang, Ruixue</creatorcontrib><creatorcontrib>Su, Yunpeng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhuang, Weiliang</au><au>Zhang, Jianjun</au><au>Pei, Lili</au><au>Fang, Shuping</au><au>Liu, Honghao</au><au>Wang, Ruixue</au><au>Su, Yunpeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Generation and characterization of human B lymphocyte stimulator blocking monoclonal antibody</atitle><jtitle>Molecular immunology</jtitle><addtitle>Mol Immunol</addtitle><date>2016-09</date><risdate>2016</risdate><volume>77</volume><spage>141</spage><epage>147</epage><pages>141-147</pages><issn>0161-5890</issn><eissn>1872-9142</eissn><abstract>•A new humanized anti-Blys antibody was developed.•The antibody binds with sub-nanomolar affinity and high specificity.•The antibody significantly inhibited Blys induced B cell proliferation, in vivo.
The cytokine, B lymphocyte stimulator (Blys) is essential for activation and proliferation of B cells and is involved in the pathogenesis of B-cell mediated autoimmune diseases. Based on its essential activity, Blys may be a potential therapeutic target for human autoimmune diseases. In this article, we have described the development of a novel humanized anti-Blys antibody, NMB04, that binds with high affinity and specificity to both soluble and membrane bound Blys. This monoclonal antibody has the potential to block Blys binding to all its three receptors, TACI, BCMA and BR-3. Further in vivo studies revealed that NMB04 possessed more potent inhibitory activity against human Blys as compared to an existing antibody, Belimumab. Therefore, NMB04 may have potential as a therapeutic candidate targeting autoimmune diseases.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>27505709</pmid><doi>10.1016/j.molimm.2016.08.002</doi><tpages>7</tpages></addata></record> |
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subjects | Animals Antibodies, Monoclonal - immunology Antibodies, Monoclonal - pharmacology Antibody Antibody Affinity - immunology Antibody Specificity - immunology Autoimmune B-Cell Activating Factor - immunology B-Lymphocytes - drug effects B-Lymphocytes - immunology Blys Enzyme-Linked Immunosorbent Assay Female Humans Lymphocyte Activation - drug effects Lymphocyte Activation - immunology Macaca fascicularis Male Mice Mice, Inbred BALB C Polymerase Chain Reaction SLE |
title | Generation and characterization of human B lymphocyte stimulator blocking monoclonal antibody |
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