Mining Naïve Rabbit Antibody Repertoires by Phage Display for Monoclonal Antibodies of Therapeutic Utility
Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but, in some cases, also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large...
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| Veröffentlicht in: | Journal of molecular biology 2017-09, Vol.429 (19), p.2954-2973 |
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| container_title | Journal of molecular biology |
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| creator | Peng, Haiyong Nerreter, Thomas Chang, Jing Qi, Junpeng Li, Xiuling Karunadharma, Pabalu Martinez, Gustavo J. Fallahi, Mohammad Soden, Jo Freeth, Jim Beerli, Roger R. Grawunder, Ulf Hudecek, Michael Rader, Christoph |
| description | Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but, in some cases, also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity. Moreover, ROR1- and ROR2-targeting rabbit mAbs demonstrated therapeutic utility as components of chimeric antigen receptor-engineered T cells, further corroborating the value of the naïve rabbit antibody library as a rich and virtually unlimited source of rabbit mAbs.
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•Generation and validation of a highly diverse naïve rabbit mAb library•>10 billion chimeric rabbit/human Fab clones minable by phage display•Selection of ROR1 and ROR2 mAbs of high diversity, affinity, and specificity•Conversion of ROR1 and ROR2 mAbs to highly potent CAR-Ts |
| doi_str_mv | 10.1016/j.jmb.2017.08.003 |
| format | Article |
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[Display omitted]
•Generation and validation of a highly diverse naïve rabbit mAb library•>10 billion chimeric rabbit/human Fab clones minable by phage display•Selection of ROR1 and ROR2 mAbs of high diversity, affinity, and specificity•Conversion of ROR1 and ROR2 mAbs to highly potent CAR-Ts</description><identifier>ISSN: 0022-2836</identifier><identifier>EISSN: 1089-8638</identifier><identifier>DOI: 10.1016/j.jmb.2017.08.003</identifier><identifier>PMID: 28818634</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antibodies, Monoclonal - isolation & purification ; Antibodies, Monoclonal - therapeutic use ; antibody engineering ; antigens ; Antigens, Neoplasm - immunology ; bacteriophages ; cancer therapy ; Cell Line, Tumor ; Cell Proliferation ; chimeric antigen receptors ; Cytokines - metabolism ; Cytotoxicity Tests, Immunologic ; high-throughput nucleotide sequencing ; Humans ; immunization ; Immunoglobulin Fab Fragments - genetics ; Immunologic Factors - isolation & purification ; Immunologic Factors - therapeutic use ; Immunotherapy - methods ; monoclonal antibodies ; neoplasms ; Peptide Library ; Rabbits ; Receptor Tyrosine Kinase-like Orphan Receptors - immunology ; Recombinant Proteins - isolation & purification ; Recombinant Proteins - therapeutic use ; ROR1 ; ROR2 ; T-lymphocytes ; T-Lymphocytes - immunology</subject><ispartof>Journal of molecular biology, 2017-09, Vol.429 (19), p.2954-2973</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-56a1a2a78c745476d341fbaa8b2011a0492d04fb648493214478ed94f9eb022f3</citedby><cites>FETCH-LOGICAL-c484t-56a1a2a78c745476d341fbaa8b2011a0492d04fb648493214478ed94f9eb022f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jmb.2017.08.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28818634$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peng, Haiyong</creatorcontrib><creatorcontrib>Nerreter, Thomas</creatorcontrib><creatorcontrib>Chang, Jing</creatorcontrib><creatorcontrib>Qi, Junpeng</creatorcontrib><creatorcontrib>Li, Xiuling</creatorcontrib><creatorcontrib>Karunadharma, Pabalu</creatorcontrib><creatorcontrib>Martinez, Gustavo J.</creatorcontrib><creatorcontrib>Fallahi, Mohammad</creatorcontrib><creatorcontrib>Soden, Jo</creatorcontrib><creatorcontrib>Freeth, Jim</creatorcontrib><creatorcontrib>Beerli, Roger R.</creatorcontrib><creatorcontrib>Grawunder, Ulf</creatorcontrib><creatorcontrib>Hudecek, Michael</creatorcontrib><creatorcontrib>Rader, Christoph</creatorcontrib><title>Mining Naïve Rabbit Antibody Repertoires by Phage Display for Monoclonal Antibodies of Therapeutic Utility</title><title>Journal of molecular biology</title><addtitle>J Mol Biol</addtitle><description>Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but, in some cases, also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity. Moreover, ROR1- and ROR2-targeting rabbit mAbs demonstrated therapeutic utility as components of chimeric antigen receptor-engineered T cells, further corroborating the value of the naïve rabbit antibody library as a rich and virtually unlimited source of rabbit mAbs.
[Display omitted]
•Generation and validation of a highly diverse naïve rabbit mAb library•>10 billion chimeric rabbit/human Fab clones minable by phage display•Selection of ROR1 and ROR2 mAbs of high diversity, affinity, and specificity•Conversion of ROR1 and ROR2 mAbs to highly potent CAR-Ts</description><subject>Animals</subject><subject>Antibodies, Monoclonal - isolation & purification</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>antibody engineering</subject><subject>antigens</subject><subject>Antigens, Neoplasm - immunology</subject><subject>bacteriophages</subject><subject>cancer therapy</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>chimeric antigen receptors</subject><subject>Cytokines - metabolism</subject><subject>Cytotoxicity Tests, Immunologic</subject><subject>high-throughput nucleotide sequencing</subject><subject>Humans</subject><subject>immunization</subject><subject>Immunoglobulin Fab Fragments - genetics</subject><subject>Immunologic Factors - isolation & purification</subject><subject>Immunologic Factors - therapeutic use</subject><subject>Immunotherapy - methods</subject><subject>monoclonal antibodies</subject><subject>neoplasms</subject><subject>Peptide Library</subject><subject>Rabbits</subject><subject>Receptor Tyrosine Kinase-like Orphan Receptors - immunology</subject><subject>Recombinant Proteins - isolation & purification</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>ROR1</subject><subject>ROR2</subject><subject>T-lymphocytes</subject><subject>T-Lymphocytes - immunology</subject><issn>0022-2836</issn><issn>1089-8638</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu1DAUhi0EokPhAdggL9kk9S2JIySkqlyK1AKq2rVlOyczHjJxantGylPxELwYHk1b0Q1deXG-_5fP-RB6S0lJCa1P1uV6Y0pGaFMSWRLCn6EFJbItZM3lc7QghLGCSV4foVcxrgkhFRfyJTpiUtLMiAX6delGNy7xd_3n9w7wlTbGJXw6Jmd8N-MrmCAk7wJEbGb8c6WXgD-5OA16xr0P-NKP3g5-1MN9yGXU9_h6BUFPsE3O4pvkBpfm1-hFr4cIb-7eY3Tz5fP12Xlx8ePrt7PTi8IKKVJR1ZpqphtpG1GJpu64oL3RWpq8KdVEtKwjojd1plvOqBCNhK4VfQsmL9zzY_Tx0DttzQY6C2MKelBTcBsdZuW1U48no1uppd-pqqak5U0ueH9XEPztFmJSGxctDIMewW-jYvmOLakqzp5EacuJkFzKPUoPqA0-xgD9w48oUXufaq2yT7X3qYhU2WfOvPt3lYfEvcAMfDgAkA-6cxBUtA5GC112ZpPqvPtP_V9xXrIm</recordid><startdate>20170915</startdate><enddate>20170915</enddate><creator>Peng, Haiyong</creator><creator>Nerreter, Thomas</creator><creator>Chang, Jing</creator><creator>Qi, Junpeng</creator><creator>Li, Xiuling</creator><creator>Karunadharma, Pabalu</creator><creator>Martinez, Gustavo J.</creator><creator>Fallahi, Mohammad</creator><creator>Soden, Jo</creator><creator>Freeth, Jim</creator><creator>Beerli, Roger R.</creator><creator>Grawunder, Ulf</creator><creator>Hudecek, Michael</creator><creator>Rader, Christoph</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><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20170915</creationdate><title>Mining Naïve Rabbit Antibody Repertoires by Phage Display for Monoclonal Antibodies of Therapeutic Utility</title><author>Peng, Haiyong ; Nerreter, Thomas ; Chang, Jing ; Qi, Junpeng ; Li, Xiuling ; Karunadharma, Pabalu ; Martinez, Gustavo J. ; Fallahi, Mohammad ; Soden, Jo ; Freeth, Jim ; Beerli, Roger R. ; Grawunder, Ulf ; Hudecek, Michael ; Rader, Christoph</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c484t-56a1a2a78c745476d341fbaa8b2011a0492d04fb648493214478ed94f9eb022f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - isolation & purification</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>antibody engineering</topic><topic>antigens</topic><topic>Antigens, Neoplasm - immunology</topic><topic>bacteriophages</topic><topic>cancer therapy</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>chimeric antigen receptors</topic><topic>Cytokines - metabolism</topic><topic>Cytotoxicity Tests, Immunologic</topic><topic>high-throughput nucleotide sequencing</topic><topic>Humans</topic><topic>immunization</topic><topic>Immunoglobulin Fab Fragments - genetics</topic><topic>Immunologic Factors - isolation & purification</topic><topic>Immunologic Factors - therapeutic use</topic><topic>Immunotherapy - methods</topic><topic>monoclonal antibodies</topic><topic>neoplasms</topic><topic>Peptide Library</topic><topic>Rabbits</topic><topic>Receptor Tyrosine Kinase-like Orphan Receptors - immunology</topic><topic>Recombinant Proteins - isolation & purification</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>ROR1</topic><topic>ROR2</topic><topic>T-lymphocytes</topic><topic>T-Lymphocytes - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peng, Haiyong</creatorcontrib><creatorcontrib>Nerreter, Thomas</creatorcontrib><creatorcontrib>Chang, Jing</creatorcontrib><creatorcontrib>Qi, Junpeng</creatorcontrib><creatorcontrib>Li, Xiuling</creatorcontrib><creatorcontrib>Karunadharma, Pabalu</creatorcontrib><creatorcontrib>Martinez, Gustavo J.</creatorcontrib><creatorcontrib>Fallahi, Mohammad</creatorcontrib><creatorcontrib>Soden, Jo</creatorcontrib><creatorcontrib>Freeth, Jim</creatorcontrib><creatorcontrib>Beerli, Roger R.</creatorcontrib><creatorcontrib>Grawunder, Ulf</creatorcontrib><creatorcontrib>Hudecek, Michael</creatorcontrib><creatorcontrib>Rader, Christoph</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><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peng, Haiyong</au><au>Nerreter, Thomas</au><au>Chang, Jing</au><au>Qi, Junpeng</au><au>Li, Xiuling</au><au>Karunadharma, Pabalu</au><au>Martinez, Gustavo J.</au><au>Fallahi, Mohammad</au><au>Soden, Jo</au><au>Freeth, Jim</au><au>Beerli, Roger R.</au><au>Grawunder, Ulf</au><au>Hudecek, Michael</au><au>Rader, Christoph</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mining Naïve Rabbit Antibody Repertoires by Phage Display for Monoclonal Antibodies of Therapeutic Utility</atitle><jtitle>Journal of molecular biology</jtitle><addtitle>J Mol Biol</addtitle><date>2017-09-15</date><risdate>2017</risdate><volume>429</volume><issue>19</issue><spage>2954</spage><epage>2973</epage><pages>2954-2973</pages><issn>0022-2836</issn><eissn>1089-8638</eissn><abstract>Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but, in some cases, also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity. Moreover, ROR1- and ROR2-targeting rabbit mAbs demonstrated therapeutic utility as components of chimeric antigen receptor-engineered T cells, further corroborating the value of the naïve rabbit antibody library as a rich and virtually unlimited source of rabbit mAbs.
[Display omitted]
•Generation and validation of a highly diverse naïve rabbit mAb library•>10 billion chimeric rabbit/human Fab clones minable by phage display•Selection of ROR1 and ROR2 mAbs of high diversity, affinity, and specificity•Conversion of ROR1 and ROR2 mAbs to highly potent CAR-Ts</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28818634</pmid><doi>10.1016/j.jmb.2017.08.003</doi><tpages>20</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies, Monoclonal - isolation & purification Antibodies, Monoclonal - therapeutic use antibody engineering antigens Antigens, Neoplasm - immunology bacteriophages cancer therapy Cell Line, Tumor Cell Proliferation chimeric antigen receptors Cytokines - metabolism Cytotoxicity Tests, Immunologic high-throughput nucleotide sequencing Humans immunization Immunoglobulin Fab Fragments - genetics Immunologic Factors - isolation & purification Immunologic Factors - therapeutic use Immunotherapy - methods monoclonal antibodies neoplasms Peptide Library Rabbits Receptor Tyrosine Kinase-like Orphan Receptors - immunology Recombinant Proteins - isolation & purification Recombinant Proteins - therapeutic use ROR1 ROR2 T-lymphocytes T-Lymphocytes - immunology |
| title | Mining Naïve Rabbit Antibody Repertoires by Phage Display for Monoclonal Antibodies of Therapeutic Utility |
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