Analysis of the Mechanism of Action of Anti‐human Interleukin‐6 and Anti‐human Interleukin‐6 Receptor‐neutralising Monoclonal Antibodies
Anti‐human interleukin‐6 (human IL‐6) and anti‐human IL‐6 receptor (IL‐6R)‐neutralising monoclonal antibodies (mAbs) are among the most promising human lL‐6‐specific inhibitors and have been shown to exert short‐term beneficial effects in clinical trials. Simultaneous treatment with different anti‐h...
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| Veröffentlicht in: | European journal of biochemistry 1997-11, Vol.249 (3), p.690-700 |
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| creator | Kalai, Michael Montero‐julian, Fèlix A. Brakenhoff, Just P. J. Fontaine, Véronique Wit, Lucas Wollmer, Axel Brailly, Hervé Content, Jean Grötzinger, Joachim |
| description | Anti‐human interleukin‐6 (human IL‐6) and anti‐human IL‐6 receptor (IL‐6R)‐neutralising monoclonal antibodies (mAbs) are among the most promising human lL‐6‐specific inhibitors and have been shown to exert short‐term beneficial effects in clinical trials. Simultaneous treatment with different anti‐human IL‐6 or anti‐human IL‐6R mAbs was recently suggested to be a potent way to inhibit the action of the cytokine in vivo. Although some of these mAbs are already used, their mechanisms of action and the location of their epitopes on the surface of human IL‐6 and human IL‐6R are still unknown. Here, we analysed the capacity of several anti‐human IL‐6 and anti‐human IL‐6R mAbs to inhibit the interaction between human IL‐6, human IL‐6R, and human glycoprotein 130 (gp130). We mapped the epitopes of several of these mAbs by studying their binding to human IL‐6 and human IL‐6R mutant proteins. Our results show that several anti‐human IL‐6 and anti‐human IL‐6R‐neutralising mAbs block the binding between human IL‐6 and human IL‐6R, whereas others block the binding to gpl 30. We provide evidence that some of the latter mAbs inhibit interaction with gp130β1, whereas others interfere with the binding to gp130β2. Our results suggest that residues included in the C′D′ loop of human IL‐6R interact with gp130β2. |
| doi_str_mv | 10.1111/j.1432-1033.1997.t01-2-00690.x |
| format | Article |
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Here, we analysed the capacity of several anti‐human IL‐6 and anti‐human IL‐6R mAbs to inhibit the interaction between human IL‐6, human IL‐6R, and human glycoprotein 130 (gp130). We mapped the epitopes of several of these mAbs by studying their binding to human IL‐6 and human IL‐6R mutant proteins. Our results show that several anti‐human IL‐6 and anti‐human IL‐6R‐neutralising mAbs block the binding between human IL‐6 and human IL‐6R, whereas others block the binding to gpl 30. We provide evidence that some of the latter mAbs inhibit interaction with gp130β1, whereas others interfere with the binding to gp130β2. Our results suggest that residues included in the C′D′ loop of human IL‐6R interact with gp130β2.</description><identifier>ISSN: 0014-2956</identifier><identifier>EISSN: 1432-1033</identifier><identifier>DOI: 10.1111/j.1432-1033.1997.t01-2-00690.x</identifier><identifier>PMID: 9395315</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Animals ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - metabolism ; Antibodies, Monoclonal - pharmacology ; Antigens, CD - metabolism ; Antigens, CD - pharmacology ; Cell Line ; Cytokine Receptor gp130 ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Epitope Mapping ; glycoprotein 130 ; Humans ; Interleukin-6 - antagonists & inhibitors ; Interleukin-6 - chemistry ; Interleukin-6 - genetics ; Interleukin-6 - immunology ; Interleukin-6 - metabolism ; interleukin‐6 ; interleukin‐6 receptor ; Membrane Glycoproteins - metabolism ; Membrane Glycoproteins - pharmacology ; Mice ; Models, Molecular ; monoclonal antibody ; Neutralization Tests ; Precipitin Tests ; Protein Conformation ; Protein Structure, Tertiary ; Receptors, Interleukin-6 - antagonists & inhibitors ; Receptors, Interleukin-6 - chemistry ; Receptors, Interleukin-6 - genetics ; Receptors, Interleukin-6 - immunology ; Receptors, Interleukin-6 - metabolism</subject><ispartof>European journal of biochemistry, 1997-11, Vol.249 (3), p.690-700</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4690-8f7b0159202a28c85732b944d11ec644d5f660a1db07f0ad2b2ed6fe4ab7bdc73</citedby><cites>FETCH-LOGICAL-c4690-8f7b0159202a28c85732b944d11ec644d5f660a1db07f0ad2b2ed6fe4ab7bdc73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1432-1033.1997.t01-2-00690.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1432-1033.1997.t01-2-00690.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9395315$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kalai, Michael</creatorcontrib><creatorcontrib>Montero‐julian, Fèlix A.</creatorcontrib><creatorcontrib>Brakenhoff, Just P. J.</creatorcontrib><creatorcontrib>Fontaine, Véronique</creatorcontrib><creatorcontrib>Wit, Lucas</creatorcontrib><creatorcontrib>Wollmer, Axel</creatorcontrib><creatorcontrib>Brailly, Hervé</creatorcontrib><creatorcontrib>Content, Jean</creatorcontrib><creatorcontrib>Grötzinger, Joachim</creatorcontrib><title>Analysis of the Mechanism of Action of Anti‐human Interleukin‐6 and Anti‐human Interleukin‐6 Receptor‐neutralising Monoclonal Antibodies</title><title>European journal of biochemistry</title><addtitle>Eur J Biochem</addtitle><description>Anti‐human interleukin‐6 (human IL‐6) and anti‐human IL‐6 receptor (IL‐6R)‐neutralising monoclonal antibodies (mAbs) are among the most promising human lL‐6‐specific inhibitors and have been shown to exert short‐term beneficial effects in clinical trials. Simultaneous treatment with different anti‐human IL‐6 or anti‐human IL‐6R mAbs was recently suggested to be a potent way to inhibit the action of the cytokine in vivo. Although some of these mAbs are already used, their mechanisms of action and the location of their epitopes on the surface of human IL‐6 and human IL‐6R are still unknown. Here, we analysed the capacity of several anti‐human IL‐6 and anti‐human IL‐6R mAbs to inhibit the interaction between human IL‐6, human IL‐6R, and human glycoprotein 130 (gp130). We mapped the epitopes of several of these mAbs by studying their binding to human IL‐6 and human IL‐6R mutant proteins. Our results show that several anti‐human IL‐6 and anti‐human IL‐6R‐neutralising mAbs block the binding between human IL‐6 and human IL‐6R, whereas others block the binding to gpl 30. We provide evidence that some of the latter mAbs inhibit interaction with gp130β1, whereas others interfere with the binding to gp130β2. Our results suggest that residues included in the C′D′ loop of human IL‐6R interact with gp130β2.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Monoclonal - metabolism</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antigens, CD - metabolism</subject><subject>Antigens, CD - pharmacology</subject><subject>Cell Line</subject><subject>Cytokine Receptor gp130</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epitope Mapping</subject><subject>glycoprotein 130</subject><subject>Humans</subject><subject>Interleukin-6 - antagonists & inhibitors</subject><subject>Interleukin-6 - chemistry</subject><subject>Interleukin-6 - genetics</subject><subject>Interleukin-6 - immunology</subject><subject>Interleukin-6 - metabolism</subject><subject>interleukin‐6</subject><subject>interleukin‐6 receptor</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Membrane Glycoproteins - pharmacology</subject><subject>Mice</subject><subject>Models, Molecular</subject><subject>monoclonal antibody</subject><subject>Neutralization Tests</subject><subject>Precipitin Tests</subject><subject>Protein Conformation</subject><subject>Protein Structure, Tertiary</subject><subject>Receptors, Interleukin-6 - antagonists & inhibitors</subject><subject>Receptors, Interleukin-6 - chemistry</subject><subject>Receptors, Interleukin-6 - genetics</subject><subject>Receptors, Interleukin-6 - immunology</subject><subject>Receptors, Interleukin-6 - metabolism</subject><issn>0014-2956</issn><issn>1432-1033</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkUlOwzAUhi0EgjIcASkrdgm2k9jNBqlUTFIrJIa15Tgv1CWxS5wIuuMIiCNyEpy2YgnCmzf977etD6ETgiPiz-k8IklMQ4LjOCJZxqMWk5CGGLMMR29baPAz3kYDjEkS0ixle2jfuTnuVYzvot0sztKYpAP0OTKyWjrtAlsG7QyCKaiZNNrVfWOkWm3NKjOt_nr_mHW1NMGNaaGpoHvWxvdYIE3xu-AOFCxa2_jCQNc2stJOm6dgao1VlfVPWO3nttDgDtFOKSsHR5t4gB4vLx7G1-Hk9upmPJqEKvF_DYclzzFJM4qppEM1THlM8yxJCkJAMR_TkjEsSZFjXmJZ0JxCwUpIZM7zQvH4AJ2sfReNfenAtaLWTkFVSQO2c4J7M8IS_KeQMMopS4kXnq2FqrHONVCKRaNr2SwFwaKnJ-aixyN6PKKnJzw9QcWKnnjzBsebm7q8huJnfYPLz8fr-auuYPlPd3F5cX7vs_gbwEeyoA</recordid><startdate>199711</startdate><enddate>199711</enddate><creator>Kalai, Michael</creator><creator>Montero‐julian, Fèlix A.</creator><creator>Brakenhoff, Just P. 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J.</creatorcontrib><creatorcontrib>Fontaine, Véronique</creatorcontrib><creatorcontrib>Wit, Lucas</creatorcontrib><creatorcontrib>Wollmer, Axel</creatorcontrib><creatorcontrib>Brailly, Hervé</creatorcontrib><creatorcontrib>Content, Jean</creatorcontrib><creatorcontrib>Grötzinger, Joachim</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kalai, Michael</au><au>Montero‐julian, Fèlix A.</au><au>Brakenhoff, Just P. J.</au><au>Fontaine, Véronique</au><au>Wit, Lucas</au><au>Wollmer, Axel</au><au>Brailly, Hervé</au><au>Content, Jean</au><au>Grötzinger, Joachim</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of the Mechanism of Action of Anti‐human Interleukin‐6 and Anti‐human Interleukin‐6 Receptor‐neutralising Monoclonal Antibodies</atitle><jtitle>European journal of biochemistry</jtitle><addtitle>Eur J Biochem</addtitle><date>1997-11</date><risdate>1997</risdate><volume>249</volume><issue>3</issue><spage>690</spage><epage>700</epage><pages>690-700</pages><issn>0014-2956</issn><eissn>1432-1033</eissn><abstract>Anti‐human interleukin‐6 (human IL‐6) and anti‐human IL‐6 receptor (IL‐6R)‐neutralising monoclonal antibodies (mAbs) are among the most promising human lL‐6‐specific inhibitors and have been shown to exert short‐term beneficial effects in clinical trials. Simultaneous treatment with different anti‐human IL‐6 or anti‐human IL‐6R mAbs was recently suggested to be a potent way to inhibit the action of the cytokine in vivo. Although some of these mAbs are already used, their mechanisms of action and the location of their epitopes on the surface of human IL‐6 and human IL‐6R are still unknown. Here, we analysed the capacity of several anti‐human IL‐6 and anti‐human IL‐6R mAbs to inhibit the interaction between human IL‐6, human IL‐6R, and human glycoprotein 130 (gp130). We mapped the epitopes of several of these mAbs by studying their binding to human IL‐6 and human IL‐6R mutant proteins. Our results show that several anti‐human IL‐6 and anti‐human IL‐6R‐neutralising mAbs block the binding between human IL‐6 and human IL‐6R, whereas others block the binding to gpl 30. We provide evidence that some of the latter mAbs inhibit interaction with gp130β1, whereas others interfere with the binding to gp130β2. Our results suggest that residues included in the C′D′ loop of human IL‐6R interact with gp130β2.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>9395315</pmid><doi>10.1111/j.1432-1033.1997.t01-2-00690.x</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-2956 |
| ispartof | European journal of biochemistry, 1997-11, Vol.249 (3), p.690-700 |
| issn | 0014-2956 1432-1033 |
| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | Animals Antibodies, Monoclonal - immunology Antibodies, Monoclonal - metabolism Antibodies, Monoclonal - pharmacology Antigens, CD - metabolism Antigens, CD - pharmacology Cell Line Cytokine Receptor gp130 Electrophoresis, Polyacrylamide Gel Enzyme-Linked Immunosorbent Assay Epitope Mapping glycoprotein 130 Humans Interleukin-6 - antagonists & inhibitors Interleukin-6 - chemistry Interleukin-6 - genetics Interleukin-6 - immunology Interleukin-6 - metabolism interleukin‐6 interleukin‐6 receptor Membrane Glycoproteins - metabolism Membrane Glycoproteins - pharmacology Mice Models, Molecular monoclonal antibody Neutralization Tests Precipitin Tests Protein Conformation Protein Structure, Tertiary Receptors, Interleukin-6 - antagonists & inhibitors Receptors, Interleukin-6 - chemistry Receptors, Interleukin-6 - genetics Receptors, Interleukin-6 - immunology Receptors, Interleukin-6 - metabolism |
| title | Analysis of the Mechanism of Action of Anti‐human Interleukin‐6 and Anti‐human Interleukin‐6 Receptor‐neutralising Monoclonal Antibodies |
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