Interleukin-6 as a therapeutic target
Human IL6 is a cytokine produced by many cell types that has pleiotropic effects. In agreement, anti-IL6 therapy reduces inflammation, hepatic acute phase proteins, and anemia and has antiangiogenic effects. Blocking IL6 has demonstrated therapeutic efficacy with drug registration in Castleman disea...
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Veröffentlicht in: | Clinical cancer research 2015-03, Vol.21 (6), p.1248-1257 |
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creator | Rossi, Jean-François Lu, Zhao-Yang Jourdan, Michel Klein, Bernard |
description | Human IL6 is a cytokine produced by many cell types that has pleiotropic effects. In agreement, anti-IL6 therapy reduces inflammation, hepatic acute phase proteins, and anemia and has antiangiogenic effects. Blocking IL6 has demonstrated therapeutic efficacy with drug registration in Castleman disease and inflammatory diseases (rheumatoid arthritis) without major toxicity. Interestingly, the inhibition of C-reactive protein (CRP) production is a trustworthy surrogate marker of anti-IL6 therapy efficacy. Clinically registered IL6 inhibitors include siltuximab, an anti-IL6 mAb, and tocilizumab, an anti-IL6R mAb. In various cancers, in particular plasma cell cancers, large randomized trials showed no efficacy of IL6 inhibitors, despite a full inhibition of CRP production in treated patients in vivo, the numerous data showing an involvement of IL6 in these diseases, and initial short-term treatments demonstrating a dramatic inhibition of cancer cell proliferation in vivo. A likely explanation is the plasticity of cancer cells, with the presence of various subclones, making the outgrowth of cancer subclones possible using growth factors other than IL6. In addition, current therapeutic strategies used in these cancers already target IL6 activity. Thus, anti-IL6 therapeutics are able to neutralize IL6 production in vivo and are safe and useful in inflammatory diseases and Castleman disease. |
doi_str_mv | 10.1158/1078-0432.CCR-14-2291 |
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In agreement, anti-IL6 therapy reduces inflammation, hepatic acute phase proteins, and anemia and has antiangiogenic effects. Blocking IL6 has demonstrated therapeutic efficacy with drug registration in Castleman disease and inflammatory diseases (rheumatoid arthritis) without major toxicity. Interestingly, the inhibition of C-reactive protein (CRP) production is a trustworthy surrogate marker of anti-IL6 therapy efficacy. Clinically registered IL6 inhibitors include siltuximab, an anti-IL6 mAb, and tocilizumab, an anti-IL6R mAb. In various cancers, in particular plasma cell cancers, large randomized trials showed no efficacy of IL6 inhibitors, despite a full inhibition of CRP production in treated patients in vivo, the numerous data showing an involvement of IL6 in these diseases, and initial short-term treatments demonstrating a dramatic inhibition of cancer cell proliferation in vivo. A likely explanation is the plasticity of cancer cells, with the presence of various subclones, making the outgrowth of cancer subclones possible using growth factors other than IL6. In addition, current therapeutic strategies used in these cancers already target IL6 activity. Thus, anti-IL6 therapeutics are able to neutralize IL6 production in vivo and are safe and useful in inflammatory diseases and Castleman disease.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-14-2291</identifier><identifier>PMID: 25589616</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject>Animals ; Antibodies, Monoclonal - pharmacology ; Antibodies, Monoclonal, Humanized - pharmacology ; Arthritis, Rheumatoid - drug therapy ; Arthritis, Rheumatoid - immunology ; Biomarkers, Tumor ; C-Reactive Protein - biosynthesis ; Cancer ; Castleman Disease - drug therapy ; Castleman Disease - metabolism ; Cell Proliferation - drug effects ; Humans ; Inflammation - drug therapy ; Interleukin-6 - antagonists & inhibitors ; Life Sciences ; Mice ; Neoplasms - drug therapy ; Receptors, Interleukin-6 - antagonists & inhibitors</subject><ispartof>Clinical cancer research, 2015-03, Vol.21 (6), p.1248-1257</ispartof><rights>2015 American Association for Cancer Research.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-4434d11c142e8b2925687ec9e1525035e7609649c60cc57a3d2022161f8befbd3</citedby><cites>FETCH-LOGICAL-c508t-4434d11c142e8b2925687ec9e1525035e7609649c60cc57a3d2022161f8befbd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25589616$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.umontpellier.fr/hal-02137928$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Rossi, Jean-François</creatorcontrib><creatorcontrib>Lu, Zhao-Yang</creatorcontrib><creatorcontrib>Jourdan, Michel</creatorcontrib><creatorcontrib>Klein, Bernard</creatorcontrib><title>Interleukin-6 as a therapeutic target</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Human IL6 is a cytokine produced by many cell types that has pleiotropic effects. In agreement, anti-IL6 therapy reduces inflammation, hepatic acute phase proteins, and anemia and has antiangiogenic effects. Blocking IL6 has demonstrated therapeutic efficacy with drug registration in Castleman disease and inflammatory diseases (rheumatoid arthritis) without major toxicity. Interestingly, the inhibition of C-reactive protein (CRP) production is a trustworthy surrogate marker of anti-IL6 therapy efficacy. Clinically registered IL6 inhibitors include siltuximab, an anti-IL6 mAb, and tocilizumab, an anti-IL6R mAb. In various cancers, in particular plasma cell cancers, large randomized trials showed no efficacy of IL6 inhibitors, despite a full inhibition of CRP production in treated patients in vivo, the numerous data showing an involvement of IL6 in these diseases, and initial short-term treatments demonstrating a dramatic inhibition of cancer cell proliferation in vivo. A likely explanation is the plasticity of cancer cells, with the presence of various subclones, making the outgrowth of cancer subclones possible using growth factors other than IL6. In addition, current therapeutic strategies used in these cancers already target IL6 activity. Thus, anti-IL6 therapeutics are able to neutralize IL6 production in vivo and are safe and useful in inflammatory diseases and Castleman disease.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibodies, Monoclonal, Humanized - pharmacology</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Biomarkers, Tumor</subject><subject>C-Reactive Protein - biosynthesis</subject><subject>Cancer</subject><subject>Castleman Disease - drug therapy</subject><subject>Castleman Disease - metabolism</subject><subject>Cell Proliferation - drug effects</subject><subject>Humans</subject><subject>Inflammation - drug therapy</subject><subject>Interleukin-6 - antagonists & inhibitors</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Neoplasms - drug therapy</subject><subject>Receptors, Interleukin-6 - antagonists & inhibitors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE1Lw0AQhhdRbK3-BCUXDx627sx-ZPdYgtpCQBA9L5vNxkbTNmxSwX9vQm1PMwzvM_A-hNwCmwNI_Qgs1ZQJjvMse6MgKKKBMzIFKVPKUcnzYT9mJuSq674YAwFMXJIJSqmNAjUl96ttH2IT9t_1lqrEdYlL-nWIrg37vvZJ7-Jn6K_JReWaLtz8zxn5eH56z5Y0f31ZZYucesl0T4XgogTwIDDoAg1KpdPgTQCJknEZUsWMEsYr5r1MHS-RIYKCShehKko-Iw-Hv2vX2DbWGxd_7c7VdrnI7XhjCDw1qH9gyMpD1sdd18VQnQBgdlRkx_p2rG8HRRaEHRUN3N2Ba_fFJpQn6uiE_wFNv16Q</recordid><startdate>20150315</startdate><enddate>20150315</enddate><creator>Rossi, Jean-François</creator><creator>Lu, Zhao-Yang</creator><creator>Jourdan, Michel</creator><creator>Klein, Bernard</creator><general>American Association for Cancer Research</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>1XC</scope></search><sort><creationdate>20150315</creationdate><title>Interleukin-6 as a therapeutic target</title><author>Rossi, Jean-François ; Lu, Zhao-Yang ; Jourdan, Michel ; Klein, Bernard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c508t-4434d11c142e8b2925687ec9e1525035e7609649c60cc57a3d2022161f8befbd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antibodies, Monoclonal, Humanized - pharmacology</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Biomarkers, Tumor</topic><topic>C-Reactive Protein - biosynthesis</topic><topic>Cancer</topic><topic>Castleman Disease - drug therapy</topic><topic>Castleman Disease - metabolism</topic><topic>Cell Proliferation - drug effects</topic><topic>Humans</topic><topic>Inflammation - drug therapy</topic><topic>Interleukin-6 - antagonists & inhibitors</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Neoplasms - drug therapy</topic><topic>Receptors, Interleukin-6 - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rossi, Jean-François</creatorcontrib><creatorcontrib>Lu, Zhao-Yang</creatorcontrib><creatorcontrib>Jourdan, Michel</creatorcontrib><creatorcontrib>Klein, Bernard</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rossi, Jean-François</au><au>Lu, Zhao-Yang</au><au>Jourdan, Michel</au><au>Klein, Bernard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-6 as a therapeutic target</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2015-03-15</date><risdate>2015</risdate><volume>21</volume><issue>6</issue><spage>1248</spage><epage>1257</epage><pages>1248-1257</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Human IL6 is a cytokine produced by many cell types that has pleiotropic effects. In agreement, anti-IL6 therapy reduces inflammation, hepatic acute phase proteins, and anemia and has antiangiogenic effects. Blocking IL6 has demonstrated therapeutic efficacy with drug registration in Castleman disease and inflammatory diseases (rheumatoid arthritis) without major toxicity. Interestingly, the inhibition of C-reactive protein (CRP) production is a trustworthy surrogate marker of anti-IL6 therapy efficacy. Clinically registered IL6 inhibitors include siltuximab, an anti-IL6 mAb, and tocilizumab, an anti-IL6R mAb. In various cancers, in particular plasma cell cancers, large randomized trials showed no efficacy of IL6 inhibitors, despite a full inhibition of CRP production in treated patients in vivo, the numerous data showing an involvement of IL6 in these diseases, and initial short-term treatments demonstrating a dramatic inhibition of cancer cell proliferation in vivo. A likely explanation is the plasticity of cancer cells, with the presence of various subclones, making the outgrowth of cancer subclones possible using growth factors other than IL6. In addition, current therapeutic strategies used in these cancers already target IL6 activity. Thus, anti-IL6 therapeutics are able to neutralize IL6 production in vivo and are safe and useful in inflammatory diseases and Castleman disease.</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>25589616</pmid><doi>10.1158/1078-0432.CCR-14-2291</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal, Humanized - pharmacology Arthritis, Rheumatoid - drug therapy Arthritis, Rheumatoid - immunology Biomarkers, Tumor C-Reactive Protein - biosynthesis Cancer Castleman Disease - drug therapy Castleman Disease - metabolism Cell Proliferation - drug effects Humans Inflammation - drug therapy Interleukin-6 - antagonists & inhibitors Life Sciences Mice Neoplasms - drug therapy Receptors, Interleukin-6 - antagonists & inhibitors |
title | Interleukin-6 as a therapeutic target |
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