Chimeric and humanized antibodies with specificity for the CD33 antigen
L and H chain cDNAs of M195, a murine mAb that binds to the CD33 Ag on normal and leukemic myeloid cells, were cloned. The cDNAs were used in the construction of mouse/human IgG1 and IgG3 chimeric antibodies. In addition, humanized antibodies were constructed which combined the complementarity-deter...
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Veröffentlicht in: | The Journal of immunology (1950) 1992-02, Vol.148 (4), p.1149-1154 |
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creator | Co, MS Avdalovic, NM Caron, PC Avdalovic, MV Scheinberg, DA Queen, C |
description | L and H chain cDNAs of M195, a murine mAb that binds to the CD33 Ag on normal and leukemic myeloid cells, were cloned. The cDNAs were used in the construction of mouse/human IgG1 and IgG3 chimeric antibodies. In addition, humanized antibodies were constructed which combined the complementarity-determining regions of the M195 antibody with human framework and constant regions. The human framework was chosen to maximize homology with the M195 V domain sequence. Moreover, a computer model of M195 was used to identify several framework amino acids that are likely to interact with the complementarity-determining regions, and these residues were also retained in the humanized antibodies. Unexpectedly, the humanized IgG1 and IgG3 M195 antibodies, which have reshaped V regions, have higher apparent binding affinity for the CD33 Ag than the chimeric or mouse antibodies. |
doi_str_mv | 10.4049/jimmunol.148.4.1149 |
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The cDNAs were used in the construction of mouse/human IgG1 and IgG3 chimeric antibodies. In addition, humanized antibodies were constructed which combined the complementarity-determining regions of the M195 antibody with human framework and constant regions. The human framework was chosen to maximize homology with the M195 V domain sequence. Moreover, a computer model of M195 was used to identify several framework amino acids that are likely to interact with the complementarity-determining regions, and these residues were also retained in the humanized antibodies. Unexpectedly, the humanized IgG1 and IgG3 M195 antibodies, which have reshaped V regions, have higher apparent binding affinity for the CD33 Ag than the chimeric or mouse antibodies.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.148.4.1149</identifier><identifier>PMID: 1737932</identifier><identifier>CODEN: JOIMA3</identifier><language>eng</language><publisher>Bethesda, MD: Am Assoc Immnol</publisher><subject>Amino Acid Sequence ; Animals ; Antibodies, immunoglobulins ; Antibodies, Monoclonal - genetics ; Antibodies, Monoclonal - immunology ; Antibody Affinity ; Antigens, CD - immunology ; Antigens, Differentiation, Myelomonocytic - immunology ; Base Sequence ; Biological and medical sciences ; Cloning, Molecular ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Humans ; Immunoglobulin G - genetics ; Immunoglobulin G - immunology ; Immunoglobulin Variable Region - genetics ; Mice ; Molecular immunology ; Molecular Sequence Data ; Monoclonal antibodies ; Recombinant Fusion Proteins - immunology ; Sialic Acid Binding Ig-like Lectin 3</subject><ispartof>The Journal of immunology (1950), 1992-02, Vol.148 (4), p.1149-1154</ispartof><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-52b1ea96f01799dbaa65d54ee9846ff48401397907861efacdef764df353f7c73</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5121751$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1737932$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Co, MS</creatorcontrib><creatorcontrib>Avdalovic, NM</creatorcontrib><creatorcontrib>Caron, PC</creatorcontrib><creatorcontrib>Avdalovic, MV</creatorcontrib><creatorcontrib>Scheinberg, DA</creatorcontrib><creatorcontrib>Queen, C</creatorcontrib><title>Chimeric and humanized antibodies with specificity for the CD33 antigen</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>L and H chain cDNAs of M195, a murine mAb that binds to the CD33 Ag on normal and leukemic myeloid cells, were cloned. The cDNAs were used in the construction of mouse/human IgG1 and IgG3 chimeric antibodies. In addition, humanized antibodies were constructed which combined the complementarity-determining regions of the M195 antibody with human framework and constant regions. The human framework was chosen to maximize homology with the M195 V domain sequence. Moreover, a computer model of M195 was used to identify several framework amino acids that are likely to interact with the complementarity-determining regions, and these residues were also retained in the humanized antibodies. Unexpectedly, the humanized IgG1 and IgG3 M195 antibodies, which have reshaped V regions, have higher apparent binding affinity for the CD33 Ag than the chimeric or mouse antibodies.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies, immunoglobulins</subject><subject>Antibodies, Monoclonal - genetics</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibody Affinity</subject><subject>Antigens, CD - immunology</subject><subject>Antigens, Differentiation, Myelomonocytic - immunology</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Cloning, Molecular</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Humans</subject><subject>Immunoglobulin G - genetics</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Mice</subject><subject>Molecular immunology</subject><subject>Molecular Sequence Data</subject><subject>Monoclonal antibodies</subject><subject>Recombinant Fusion Proteins - immunology</subject><subject>Sialic Acid Binding Ig-like Lectin 3</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1P3DAQhi1UBFvgF1RIOVTtKctM7NjxES0tRULqBc6W1xkTo3wsdqKI_vqG7vbj1tNoNM_7jvQw9gFhLUDoq-fQdVM_tGsU1VqsEYU-YissS8ilBPmOrQCKIkcl1Sl7n9IzAEgoxAk7QcWV5sWK3W6a0FEMLrN9nTVTZ_vwg-plG8N2qAOlbA5jk6UdueCDC-Nr5oeYjQ1lmxvOf4FP1J-zY2_bRBeHecYev3552HzL77_f3m2u73MnuBrzstgiWS09oNK63lory7oURLoS0ntRCUCulQZVSSRvXU1eSVF7XnKvnOJn7NO-dxeHl4nSaLqQHLWt7WmYklFFBVqg_i-IEkGjhAXke9DFIaVI3uxi6Gx8NQjmzbP57dksno0wb56X1OWhftp2VP_N7MUu94-Hu03Otj7a3oX0ByuxQFXign3eY014auYQyaTOtu1Simae538e_gSJDZTK</recordid><startdate>19920215</startdate><enddate>19920215</enddate><creator>Co, MS</creator><creator>Avdalovic, NM</creator><creator>Caron, PC</creator><creator>Avdalovic, MV</creator><creator>Scheinberg, DA</creator><creator>Queen, C</creator><general>Am Assoc Immnol</general><general>American Association of Immunologists</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>19920215</creationdate><title>Chimeric and humanized antibodies with specificity for the CD33 antigen</title><author>Co, MS ; Avdalovic, NM ; Caron, PC ; Avdalovic, MV ; Scheinberg, DA ; Queen, C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-52b1ea96f01799dbaa65d54ee9846ff48401397907861efacdef764df353f7c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies, immunoglobulins</topic><topic>Antibodies, Monoclonal - genetics</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibody Affinity</topic><topic>Antigens, CD - immunology</topic><topic>Antigens, Differentiation, Myelomonocytic - immunology</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Cloning, Molecular</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Humans</topic><topic>Immunoglobulin G - genetics</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunoglobulin Variable Region - genetics</topic><topic>Mice</topic><topic>Molecular immunology</topic><topic>Molecular Sequence Data</topic><topic>Monoclonal antibodies</topic><topic>Recombinant Fusion Proteins - immunology</topic><topic>Sialic Acid Binding Ig-like Lectin 3</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Co, MS</creatorcontrib><creatorcontrib>Avdalovic, NM</creatorcontrib><creatorcontrib>Caron, PC</creatorcontrib><creatorcontrib>Avdalovic, MV</creatorcontrib><creatorcontrib>Scheinberg, DA</creatorcontrib><creatorcontrib>Queen, C</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>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Co, MS</au><au>Avdalovic, NM</au><au>Caron, PC</au><au>Avdalovic, MV</au><au>Scheinberg, DA</au><au>Queen, C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chimeric and humanized antibodies with specificity for the CD33 antigen</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>1992-02-15</date><risdate>1992</risdate><volume>148</volume><issue>4</issue><spage>1149</spage><epage>1154</epage><pages>1149-1154</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><coden>JOIMA3</coden><abstract>L and H chain cDNAs of M195, a murine mAb that binds to the CD33 Ag on normal and leukemic myeloid cells, were cloned. The cDNAs were used in the construction of mouse/human IgG1 and IgG3 chimeric antibodies. In addition, humanized antibodies were constructed which combined the complementarity-determining regions of the M195 antibody with human framework and constant regions. The human framework was chosen to maximize homology with the M195 V domain sequence. Moreover, a computer model of M195 was used to identify several framework amino acids that are likely to interact with the complementarity-determining regions, and these residues were also retained in the humanized antibodies. Unexpectedly, the humanized IgG1 and IgG3 M195 antibodies, which have reshaped V regions, have higher apparent binding affinity for the CD33 Ag than the chimeric or mouse antibodies.</abstract><cop>Bethesda, MD</cop><pub>Am Assoc Immnol</pub><pmid>1737932</pmid><doi>10.4049/jimmunol.148.4.1149</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Sequence Animals Antibodies, immunoglobulins Antibodies, Monoclonal - genetics Antibodies, Monoclonal - immunology Antibody Affinity Antigens, CD - immunology Antigens, Differentiation, Myelomonocytic - immunology Base Sequence Biological and medical sciences Cloning, Molecular Fundamental and applied biological sciences. Psychology Fundamental immunology Humans Immunoglobulin G - genetics Immunoglobulin G - immunology Immunoglobulin Variable Region - genetics Mice Molecular immunology Molecular Sequence Data Monoclonal antibodies Recombinant Fusion Proteins - immunology Sialic Acid Binding Ig-like Lectin 3 |
title | Chimeric and humanized antibodies with specificity for the CD33 antigen |
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