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Design and characterization of Zweimab and Doppelmab, high affinity dual antagonistic anti-TSLP/IL13 bispecific antibodies
Patients with severe Th2 type asthma often have a steroid resistant phenotype and are prone to acute exacerbations. Current novel therapies have only marginal therapeutic effects. One of the hypotheses for lack of major efficacy in most patients is targeting only one redundant pathway leaving others...
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| Published in: | Biochemical and biophysical research communications 2018-09, Vol.504 (1), p.19-24 |
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| Main Authors: | , , , , , , , , , , , , |
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| container_end_page | 24 |
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| container_title | Biochemical and biophysical research communications |
| container_volume | 504 |
| creator | Venkataramani, Sathyadevi Low, Sarah Weigle, Bernd Dutcher, Darrin Jerath, Kavita Menzenski, Monica Frego, Lee Truncali, Kris Gupta, Pankaj Kroe-Barrett, Rachel Ganesan, Rajkumar Singh, Sanjaya Erb, Klaus J. |
| description | Patients with severe Th2 type asthma often have a steroid resistant phenotype and are prone to acute exacerbations. Current novel therapies have only marginal therapeutic effects. One of the hypotheses for lack of major efficacy in most patients is targeting only one redundant pathway leaving others active. Hence, we have designed and developed novel highly potent bispecific anti-TSLP/IL13 antibodies called Zweimabs (monovalent bispecific) and Doppelmabs (bivalent bispecific) that concurrently inhibits the signaling by these two cytokines.
•Lack of efficacy from anti-IL13 monotherapies.•Dual targeting TSLP and IL13 due to great overlap of signaling pathways.•Design and development of Zweimab and Doppelmab bispecifics targeting TSLP and IL13.•Zweimabs and Doppelmabs are highly potent with picomolar affinity to the targets. |
| doi_str_mv | 10.1016/j.bbrc.2018.08.064 |
| format | article |
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•Lack of efficacy from anti-IL13 monotherapies.•Dual targeting TSLP and IL13 due to great overlap of signaling pathways.•Design and development of Zweimab and Doppelmab bispecifics targeting TSLP and IL13.•Zweimabs and Doppelmabs are highly potent with picomolar affinity to the targets.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2018.08.064</identifier><identifier>PMID: 30126632</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ANTIBODIES ; ASTHMA ; Bispecific ; Epitope mapping ; IL13 ; LYMPHOKINES ; PHENOTYPE ; SPR ; STEROIDS ; TSLP</subject><ispartof>Biochemical and biophysical research communications, 2018-09, Vol.504 (1), p.19-24</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-1e10873fb015e6b7c45a33250ba7a23bc51e01a1675bacc21a17260e904f69bf3</citedby><cites>FETCH-LOGICAL-c499t-1e10873fb015e6b7c45a33250ba7a23bc51e01a1675bacc21a17260e904f69bf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30126632$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/23134232$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Venkataramani, Sathyadevi</creatorcontrib><creatorcontrib>Low, Sarah</creatorcontrib><creatorcontrib>Weigle, Bernd</creatorcontrib><creatorcontrib>Dutcher, Darrin</creatorcontrib><creatorcontrib>Jerath, Kavita</creatorcontrib><creatorcontrib>Menzenski, Monica</creatorcontrib><creatorcontrib>Frego, Lee</creatorcontrib><creatorcontrib>Truncali, Kris</creatorcontrib><creatorcontrib>Gupta, Pankaj</creatorcontrib><creatorcontrib>Kroe-Barrett, Rachel</creatorcontrib><creatorcontrib>Ganesan, Rajkumar</creatorcontrib><creatorcontrib>Singh, Sanjaya</creatorcontrib><creatorcontrib>Erb, Klaus J.</creatorcontrib><title>Design and characterization of Zweimab and Doppelmab, high affinity dual antagonistic anti-TSLP/IL13 bispecific antibodies</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Patients with severe Th2 type asthma often have a steroid resistant phenotype and are prone to acute exacerbations. Current novel therapies have only marginal therapeutic effects. One of the hypotheses for lack of major efficacy in most patients is targeting only one redundant pathway leaving others active. Hence, we have designed and developed novel highly potent bispecific anti-TSLP/IL13 antibodies called Zweimabs (monovalent bispecific) and Doppelmabs (bivalent bispecific) that concurrently inhibits the signaling by these two cytokines.
•Lack of efficacy from anti-IL13 monotherapies.•Dual targeting TSLP and IL13 due to great overlap of signaling pathways.•Design and development of Zweimab and Doppelmab bispecifics targeting TSLP and IL13.•Zweimabs and Doppelmabs are highly potent with picomolar affinity to the targets.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ANTIBODIES</subject><subject>ASTHMA</subject><subject>Bispecific</subject><subject>Epitope mapping</subject><subject>IL13</subject><subject>LYMPHOKINES</subject><subject>PHENOTYPE</subject><subject>SPR</subject><subject>STEROIDS</subject><subject>TSLP</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp9kU9r3DAQxUVpaLZpv0APxdBLD_VmRrLlGHopSf8EFhJoCqUXIcnjXS1ey5W0Lcmnr9zd9FgYkIb5zeMxj7FXCEsElOfbpTHBLjngxRJyyeoJWyC0UHKE6ilbAIAseYvfT9nzGLcAiJVsn7FTAcilFHzBHq4ouvVY6LEr7EYHbRMF96CT82Ph--LHb3I7bf7Or_w00ZC7d8XGrTeF7ns3unRfdHs9ZCLptR9dTM7OjSvvvq5uz69XKArj4kTW9ceJ8Z2j-IKd9HqI9PL4nrFvnz7eXX4pVzefry8_rEpbtW0qkRAuGtEbwJqkaWxVayF4DUY3mgtjayRAjbKpjbaW52_DJVALVS9b04sz9uag67M1Fa1LZDfWjyPZpLhAUXHBM_X2QE3B_9xTTGrnoqVh0CP5fVQcWsychDqj_IDa4GMM1Ksp5COFe4Wg5mTUVs3JqDkZBblklZdeH_X3Zkfdv5XHKDLw_gBQvsUvR2G2SqOlzoXZaefd__T_AE3onr4</recordid><startdate>20180926</startdate><enddate>20180926</enddate><creator>Venkataramani, Sathyadevi</creator><creator>Low, Sarah</creator><creator>Weigle, Bernd</creator><creator>Dutcher, Darrin</creator><creator>Jerath, Kavita</creator><creator>Menzenski, Monica</creator><creator>Frego, Lee</creator><creator>Truncali, Kris</creator><creator>Gupta, Pankaj</creator><creator>Kroe-Barrett, Rachel</creator><creator>Ganesan, Rajkumar</creator><creator>Singh, Sanjaya</creator><creator>Erb, Klaus J.</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20180926</creationdate><title>Design and characterization of Zweimab and Doppelmab, high affinity dual antagonistic anti-TSLP/IL13 bispecific antibodies</title><author>Venkataramani, Sathyadevi ; Low, Sarah ; Weigle, Bernd ; Dutcher, Darrin ; Jerath, Kavita ; Menzenski, Monica ; Frego, Lee ; Truncali, Kris ; Gupta, Pankaj ; Kroe-Barrett, Rachel ; Ganesan, Rajkumar ; Singh, Sanjaya ; Erb, Klaus J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-1e10873fb015e6b7c45a33250ba7a23bc51e01a1675bacc21a17260e904f69bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ANTIBODIES</topic><topic>ASTHMA</topic><topic>Bispecific</topic><topic>Epitope mapping</topic><topic>IL13</topic><topic>LYMPHOKINES</topic><topic>PHENOTYPE</topic><topic>SPR</topic><topic>STEROIDS</topic><topic>TSLP</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Venkataramani, Sathyadevi</creatorcontrib><creatorcontrib>Low, Sarah</creatorcontrib><creatorcontrib>Weigle, Bernd</creatorcontrib><creatorcontrib>Dutcher, Darrin</creatorcontrib><creatorcontrib>Jerath, Kavita</creatorcontrib><creatorcontrib>Menzenski, Monica</creatorcontrib><creatorcontrib>Frego, Lee</creatorcontrib><creatorcontrib>Truncali, Kris</creatorcontrib><creatorcontrib>Gupta, Pankaj</creatorcontrib><creatorcontrib>Kroe-Barrett, Rachel</creatorcontrib><creatorcontrib>Ganesan, Rajkumar</creatorcontrib><creatorcontrib>Singh, Sanjaya</creatorcontrib><creatorcontrib>Erb, Klaus J.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Venkataramani, Sathyadevi</au><au>Low, Sarah</au><au>Weigle, Bernd</au><au>Dutcher, Darrin</au><au>Jerath, Kavita</au><au>Menzenski, Monica</au><au>Frego, Lee</au><au>Truncali, Kris</au><au>Gupta, Pankaj</au><au>Kroe-Barrett, Rachel</au><au>Ganesan, Rajkumar</au><au>Singh, Sanjaya</au><au>Erb, Klaus J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design and characterization of Zweimab and Doppelmab, high affinity dual antagonistic anti-TSLP/IL13 bispecific antibodies</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2018-09-26</date><risdate>2018</risdate><volume>504</volume><issue>1</issue><spage>19</spage><epage>24</epage><pages>19-24</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Patients with severe Th2 type asthma often have a steroid resistant phenotype and are prone to acute exacerbations. 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•Lack of efficacy from anti-IL13 monotherapies.•Dual targeting TSLP and IL13 due to great overlap of signaling pathways.•Design and development of Zweimab and Doppelmab bispecifics targeting TSLP and IL13.•Zweimabs and Doppelmabs are highly potent with picomolar affinity to the targets.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30126632</pmid><doi>10.1016/j.bbrc.2018.08.064</doi><tpages>6</tpages></addata></record> |
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| source | Elsevier ScienceDirect Freedom Collection 2023 |
| subjects | 60 APPLIED LIFE SCIENCES ANTIBODIES ASTHMA Bispecific Epitope mapping IL13 LYMPHOKINES PHENOTYPE SPR STEROIDS TSLP |
| title | Design and characterization of Zweimab and Doppelmab, high affinity dual antagonistic anti-TSLP/IL13 bispecific antibodies |
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