Genetically engineered deglycosylation of the variable domain increases the affinity of an anti-CD33 monoclonal antibody
M195 is a murine monoclonal antibody that binds to the CD33 antigen and is being tested for the treatment of myeloid leukemia. Surprisingly, a complementarity determining region (CDR)-grafted, humanized M195 antibody displayed a several-fold higher binding affinity for the CD33 antigen than the orig...
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| Veröffentlicht in: | Molecular immunology 1993-10, Vol.30 (15), p.1361-1367 |
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| container_title | Molecular immunology |
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| creator | Man Sung Co Scheinberg, David A. Avdalovic, Nevenka M. Mcgraw, Kimberly Vasquez, Max Caron, Philip C. Queen, Cary |
| description | M195 is a murine monoclonal antibody that binds to the CD33 antigen and is being tested for the treatment of myeloid leukemia. Surprisingly, a complementarity determining region (CDR)-grafted, humanized M195 antibody displayed a several-fold higher binding affinity for the CD33 antigen than the original murine antibody. Here we show that the increase in binding affinity resulted from eliminating an
N-linked glycosylation site at residue 73 in the heavy chain variable region in the course of humanization. Re-introducing the glycosylation site in the humanized antibody reduces its binding affinity to that of the murine antibody, while removing the glycosylation site from the murine M195 variable domain increases its affinity. The removal of variable region carbohydrates may provide a method for increasing the affinity of certain monoclonal antibodies with diagnostic and therapeutic potential. |
| doi_str_mv | 10.1016/0161-5890(93)90097-U |
| format | Article |
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N-linked glycosylation site at residue 73 in the heavy chain variable region in the course of humanization. Re-introducing the glycosylation site in the humanized antibody reduces its binding affinity to that of the murine antibody, while removing the glycosylation site from the murine M195 variable domain increases its affinity. The removal of variable region carbohydrates may provide a method for increasing the affinity of certain monoclonal antibodies with diagnostic and therapeutic potential.</description><identifier>ISSN: 0161-5890</identifier><identifier>EISSN: 1872-9142</identifier><identifier>DOI: 10.1016/0161-5890(93)90097-U</identifier><identifier>PMID: 8232322</identifier><identifier>CODEN: MOIMD5</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Amino Acid Sequence ; Antibodies, immunoglobulins ; Antibodies, Monoclonal - chemistry ; Antibodies, Monoclonal - immunology ; Antibody Affinity ; Antigens, CD - immunology ; Antigens, Differentiation, Myelomonocytic - immunology ; Binding Sites, Antibody ; Biological and medical sciences ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Glycoproteins - immunology ; Immunoglobulin Variable Region - chemistry ; Models, Molecular ; Molecular immunology ; Molecular Sequence Data ; Monoclonal antibodies ; Protein Structure, Tertiary ; Recombinant Fusion Proteins - immunology ; Sialic Acid Binding Ig-like Lectin 3 ; Structure-Activity Relationship</subject><ispartof>Molecular immunology, 1993-10, Vol.30 (15), p.1361-1367</ispartof><rights>1993</rights><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-c164e731d1fb3d50a813ab891346adbd6040136b581fc91e75b2c12b80ae6a4a3</citedby><cites>FETCH-LOGICAL-c417t-c164e731d1fb3d50a813ab891346adbd6040136b581fc91e75b2c12b80ae6a4a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0161-5890(93)90097-U$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3777651$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8232322$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Man Sung Co</creatorcontrib><creatorcontrib>Scheinberg, David A.</creatorcontrib><creatorcontrib>Avdalovic, Nevenka M.</creatorcontrib><creatorcontrib>Mcgraw, Kimberly</creatorcontrib><creatorcontrib>Vasquez, Max</creatorcontrib><creatorcontrib>Caron, Philip C.</creatorcontrib><creatorcontrib>Queen, Cary</creatorcontrib><title>Genetically engineered deglycosylation of the variable domain increases the affinity of an anti-CD33 monoclonal antibody</title><title>Molecular immunology</title><addtitle>Mol Immunol</addtitle><description>M195 is a murine monoclonal antibody that binds to the CD33 antigen and is being tested for the treatment of myeloid leukemia. Surprisingly, a complementarity determining region (CDR)-grafted, humanized M195 antibody displayed a several-fold higher binding affinity for the CD33 antigen than the original murine antibody. Here we show that the increase in binding affinity resulted from eliminating an
N-linked glycosylation site at residue 73 in the heavy chain variable region in the course of humanization. Re-introducing the glycosylation site in the humanized antibody reduces its binding affinity to that of the murine antibody, while removing the glycosylation site from the murine M195 variable domain increases its affinity. The removal of variable region carbohydrates may provide a method for increasing the affinity of certain monoclonal antibodies with diagnostic and therapeutic potential.</description><subject>Amino Acid Sequence</subject><subject>Antibodies, immunoglobulins</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibody Affinity</subject><subject>Antigens, CD - immunology</subject><subject>Antigens, Differentiation, Myelomonocytic - immunology</subject><subject>Binding Sites, Antibody</subject><subject>Biological and medical sciences</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Glycoproteins - immunology</subject><subject>Immunoglobulin Variable Region - chemistry</subject><subject>Models, Molecular</subject><subject>Molecular immunology</subject><subject>Molecular Sequence Data</subject><subject>Monoclonal antibodies</subject><subject>Protein Structure, Tertiary</subject><subject>Recombinant Fusion Proteins - immunology</subject><subject>Sialic Acid Binding Ig-like Lectin 3</subject><subject>Structure-Activity Relationship</subject><issn>0161-5890</issn><issn>1872-9142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU-LFDEQxYMo6-zqN1Dog8h6aE11upP0ZUFGXYUFL845VCfVaySTrEnPYn97e_4wRyUJBXm_Kor3GHsF_D1wkB-WB3Wne37di3c9572qN0_YCrRq6h7a5ilbnZHn7LKUX5xzyWV3wS50I5bTrNifW4o0eYshzBXFex-JMrnK0X2YbSpzwMmnWKWxmn5S9YjZ4xCocmmLPlY-2kxYqBxUHEcf_TTvaYzLnXy9_iREtU0x2ZAihsPnkNz8gj0bMRR6eapXbPPl84_11_ru--239ce72ragptqCbEkJcDAOwnUcNQgcdA-ilegGJ3nLQcih0zDaHkh1Q2OhGTRHktiiuGJvj3Mfcvq9ozKZrS-WQsBIaVeMkrzjqmn_C4LUTSe0XsD2CNqcSsk0mofst5hnA9zskzF7283edtMLc0jGbJa216f5u2FL7tx0imLR35x0LEscY8ZofTljQiklO1iwmyNGi2mPnrIp1lO05HwmOxmX_L_3-AsZGqsd</recordid><startdate>19931001</startdate><enddate>19931001</enddate><creator>Man Sung Co</creator><creator>Scheinberg, David A.</creator><creator>Avdalovic, Nevenka M.</creator><creator>Mcgraw, Kimberly</creator><creator>Vasquez, Max</creator><creator>Caron, Philip C.</creator><creator>Queen, Cary</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>19931001</creationdate><title>Genetically engineered deglycosylation of the variable domain increases the affinity of an anti-CD33 monoclonal antibody</title><author>Man Sung Co ; Scheinberg, David A. ; Avdalovic, Nevenka M. ; Mcgraw, Kimberly ; Vasquez, Max ; Caron, Philip C. ; Queen, Cary</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-c164e731d1fb3d50a813ab891346adbd6040136b581fc91e75b2c12b80ae6a4a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Amino Acid Sequence</topic><topic>Antibodies, immunoglobulins</topic><topic>Antibodies, Monoclonal - chemistry</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibody Affinity</topic><topic>Antigens, CD - immunology</topic><topic>Antigens, Differentiation, Myelomonocytic - immunology</topic><topic>Binding Sites, Antibody</topic><topic>Biological and medical sciences</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Glycoproteins - immunology</topic><topic>Immunoglobulin Variable Region - chemistry</topic><topic>Models, Molecular</topic><topic>Molecular immunology</topic><topic>Molecular Sequence Data</topic><topic>Monoclonal antibodies</topic><topic>Protein Structure, Tertiary</topic><topic>Recombinant Fusion Proteins - immunology</topic><topic>Sialic Acid Binding Ig-like Lectin 3</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Man Sung Co</creatorcontrib><creatorcontrib>Scheinberg, David A.</creatorcontrib><creatorcontrib>Avdalovic, Nevenka M.</creatorcontrib><creatorcontrib>Mcgraw, Kimberly</creatorcontrib><creatorcontrib>Vasquez, Max</creatorcontrib><creatorcontrib>Caron, Philip C.</creatorcontrib><creatorcontrib>Queen, Cary</creatorcontrib><collection>Pascal-Francis</collection><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>Molecular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Man Sung Co</au><au>Scheinberg, David A.</au><au>Avdalovic, Nevenka M.</au><au>Mcgraw, Kimberly</au><au>Vasquez, Max</au><au>Caron, Philip C.</au><au>Queen, Cary</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetically engineered deglycosylation of the variable domain increases the affinity of an anti-CD33 monoclonal antibody</atitle><jtitle>Molecular immunology</jtitle><addtitle>Mol Immunol</addtitle><date>1993-10-01</date><risdate>1993</risdate><volume>30</volume><issue>15</issue><spage>1361</spage><epage>1367</epage><pages>1361-1367</pages><issn>0161-5890</issn><eissn>1872-9142</eissn><coden>MOIMD5</coden><abstract>M195 is a murine monoclonal antibody that binds to the CD33 antigen and is being tested for the treatment of myeloid leukemia. Surprisingly, a complementarity determining region (CDR)-grafted, humanized M195 antibody displayed a several-fold higher binding affinity for the CD33 antigen than the original murine antibody. Here we show that the increase in binding affinity resulted from eliminating an
N-linked glycosylation site at residue 73 in the heavy chain variable region in the course of humanization. Re-introducing the glycosylation site in the humanized antibody reduces its binding affinity to that of the murine antibody, while removing the glycosylation site from the murine M195 variable domain increases its affinity. The removal of variable region carbohydrates may provide a method for increasing the affinity of certain monoclonal antibodies with diagnostic and therapeutic potential.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>8232322</pmid><doi>10.1016/0161-5890(93)90097-U</doi><tpages>7</tpages></addata></record> |
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| subjects | Amino Acid Sequence Antibodies, immunoglobulins Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - immunology Antibody Affinity Antigens, CD - immunology Antigens, Differentiation, Myelomonocytic - immunology Binding Sites, Antibody Biological and medical sciences Fundamental and applied biological sciences. Psychology Fundamental immunology Glycoproteins - immunology Immunoglobulin Variable Region - chemistry Models, Molecular Molecular immunology Molecular Sequence Data Monoclonal antibodies Protein Structure, Tertiary Recombinant Fusion Proteins - immunology Sialic Acid Binding Ig-like Lectin 3 Structure-Activity Relationship |
| title | Genetically engineered deglycosylation of the variable domain increases the affinity of an anti-CD33 monoclonal antibody |
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