Charge-modified single chain antibody constructs of monoclonal antibody CC49: generation, characterization, pharmacokinetics, and biodistribution analysis
A novel strategy was developed in which an antibody scFv fragment of the monoclonal antibody (MAb) CC49 was modified by engineering DNA coding sequences to lower its isoelectric point. Negatively charged amino acids were added to the carboxy terminus of the CC49 V H region by adding nucleotide seque...
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| Veröffentlicht in: | Nuclear medicine and biology 1999, Vol.26 (1), p.27-34 |
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| creator | Pavlinkova, Gabriela Beresford, Guy Booth, Barbara J.M Batra, Surinder K Colcher, David |
| description | A novel strategy was developed in which an antibody scFv fragment of the monoclonal antibody (MAb) CC49 was modified by engineering DNA coding sequences to lower its isoelectric point. Negatively charged amino acids were added to the carboxy terminus of the CC49 V
H region by adding nucleotide sequences in a polymerase chain reaction (PCR) amplification of the coding sequence of CC49 scFv. Two new DNA constructs coding for CC49 scFv with lower isoelectric points of 5.8 and 5.2 were engineered. These novel strategy-generated, charge-modified antibody constructs were compared for their immunological, pharmacokinetic, and biodistribution properties in athymic mice bearing LS-174T human colon carcinoma xenografts. |
| doi_str_mv | 10.1016/S0969-8051(98)00075-4 |
| format | Article |
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H region by adding nucleotide sequences in a polymerase chain reaction (PCR) amplification of the coding sequence of CC49 scFv. Two new DNA constructs coding for CC49 scFv with lower isoelectric points of 5.8 and 5.2 were engineered. These novel strategy-generated, charge-modified antibody constructs were compared for their immunological, pharmacokinetic, and biodistribution properties in athymic mice bearing LS-174T human colon carcinoma xenografts.</description><identifier>ISSN: 0969-8051</identifier><identifier>EISSN: 1872-9614</identifier><identifier>DOI: 10.1016/S0969-8051(98)00075-4</identifier><identifier>PMID: 10096498</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Amino Acid Sequence ; Animals ; Antibodies, Neoplasm - biosynthesis ; Antibodies, Neoplasm - metabolism ; Antibody engineering ; Antibody Formation ; Base Sequence ; Biological and medical sciences ; Carcinoma - metabolism ; Colon carcinoma xenografts ; Colonic Neoplasms - metabolism ; Digestive system ; Female ; Humans ; Immunoglobulin Variable Region ; Investigative techniques, diagnostic techniques (general aspects) ; Iodine Radioisotopes ; Isoelectric Point ; Medical sciences ; Mice ; Mice, Nude ; Molecular Sequence Data ; Neoplasm Transplantation ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Polymerase Chain Reaction ; Radioimmunodiagnosis ; Radiopharmaceuticals ; Single chain fragments</subject><ispartof>Nuclear medicine and biology, 1999, Vol.26 (1), p.27-34</ispartof><rights>1999 Elsevier Science Inc.</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-cbbac441905daca5067a8f8d9b04e40e84bd93d457be3bf0d01ec9b48853c6d3</citedby><cites>FETCH-LOGICAL-c390t-cbbac441905daca5067a8f8d9b04e40e84bd93d457be3bf0d01ec9b48853c6d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0969-8051(98)00075-4$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,4024,27923,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1681807$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10096498$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pavlinkova, Gabriela</creatorcontrib><creatorcontrib>Beresford, Guy</creatorcontrib><creatorcontrib>Booth, Barbara J.M</creatorcontrib><creatorcontrib>Batra, Surinder K</creatorcontrib><creatorcontrib>Colcher, David</creatorcontrib><title>Charge-modified single chain antibody constructs of monoclonal antibody CC49: generation, characterization, pharmacokinetics, and biodistribution analysis</title><title>Nuclear medicine and biology</title><addtitle>Nucl Med Biol</addtitle><description>A novel strategy was developed in which an antibody scFv fragment of the monoclonal antibody (MAb) CC49 was modified by engineering DNA coding sequences to lower its isoelectric point. Negatively charged amino acids were added to the carboxy terminus of the CC49 V
H region by adding nucleotide sequences in a polymerase chain reaction (PCR) amplification of the coding sequence of CC49 scFv. Two new DNA constructs coding for CC49 scFv with lower isoelectric points of 5.8 and 5.2 were engineered. These novel strategy-generated, charge-modified antibody constructs were compared for their immunological, pharmacokinetic, and biodistribution properties in athymic mice bearing LS-174T human colon carcinoma xenografts.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies, Neoplasm - biosynthesis</subject><subject>Antibodies, Neoplasm - metabolism</subject><subject>Antibody engineering</subject><subject>Antibody Formation</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Carcinoma - metabolism</subject><subject>Colon carcinoma xenografts</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Digestive system</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin Variable Region</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Iodine Radioisotopes</subject><subject>Isoelectric Point</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Molecular Sequence Data</subject><subject>Neoplasm Transplantation</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Polymerase Chain Reaction</subject><subject>Radioimmunodiagnosis</subject><subject>Radiopharmaceuticals</subject><subject>Single chain fragments</subject><issn>0969-8051</issn><issn>1872-9614</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxS0EotvCRwDlgBBIDdiNk7V7QSjin1SJA71b9niyHUjsxU6Qlo_Cp623u6LcOFl6_r03o3mMPRP8jeCie_uN607XirfilVavOefrtpYP2Eqo9UWtOyEfstVf5ISd5vydF58U_DE7Ebx8Sa1W7E9_Y9MG6yl6Ggh9lSlsRqzgxlKobJjJRb-rIIY8pwXmXMWhmmKIMMZgx3ui76W-rDYYMNmZYjjfRyQLMyb6fVS2RZksxB8UcCbI58XuK0dldkknt-yxotlxlyk_YY8GO2Z8enzP2PXHD9f95_rq66cv_furGhrN5xqcsyCl0Lz1FmzLu7VVg_LacYmSo5LO68bLdu2wcQP3XCBoJ5VqG-h8c8ZeHmK3Kf5cMM9mogw4jjZgXLLpdNfKi7YpYHsAIcWcEw5mm2iyaWcEN_tOzF0nZn9wo5W568TI4nt-HLC4Cf0_rkMJBXhxBGwGOw7JBqB8z3VKKL4u2LsDhuUYvwiTyUAYAD0lhNn4SP_Z5BbySa0f</recordid><startdate>1999</startdate><enddate>1999</enddate><creator>Pavlinkova, Gabriela</creator><creator>Beresford, Guy</creator><creator>Booth, Barbara J.M</creator><creator>Batra, Surinder K</creator><creator>Colcher, David</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>1999</creationdate><title>Charge-modified single chain antibody constructs of monoclonal antibody CC49: generation, characterization, pharmacokinetics, and biodistribution analysis</title><author>Pavlinkova, Gabriela ; Beresford, Guy ; Booth, Barbara J.M ; Batra, Surinder K ; Colcher, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-cbbac441905daca5067a8f8d9b04e40e84bd93d457be3bf0d01ec9b48853c6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies, Neoplasm - biosynthesis</topic><topic>Antibodies, Neoplasm - metabolism</topic><topic>Antibody engineering</topic><topic>Antibody Formation</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Carcinoma - metabolism</topic><topic>Colon carcinoma xenografts</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Digestive system</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoglobulin Variable Region</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Iodine Radioisotopes</topic><topic>Isoelectric Point</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Molecular Sequence Data</topic><topic>Neoplasm Transplantation</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Polymerase Chain Reaction</topic><topic>Radioimmunodiagnosis</topic><topic>Radiopharmaceuticals</topic><topic>Single chain fragments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pavlinkova, Gabriela</creatorcontrib><creatorcontrib>Beresford, Guy</creatorcontrib><creatorcontrib>Booth, Barbara J.M</creatorcontrib><creatorcontrib>Batra, Surinder K</creatorcontrib><creatorcontrib>Colcher, David</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>MEDLINE - Academic</collection><jtitle>Nuclear medicine and biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pavlinkova, Gabriela</au><au>Beresford, Guy</au><au>Booth, Barbara J.M</au><au>Batra, Surinder K</au><au>Colcher, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Charge-modified single chain antibody constructs of monoclonal antibody CC49: generation, characterization, pharmacokinetics, and biodistribution analysis</atitle><jtitle>Nuclear medicine and biology</jtitle><addtitle>Nucl Med Biol</addtitle><date>1999</date><risdate>1999</risdate><volume>26</volume><issue>1</issue><spage>27</spage><epage>34</epage><pages>27-34</pages><issn>0969-8051</issn><eissn>1872-9614</eissn><abstract>A novel strategy was developed in which an antibody scFv fragment of the monoclonal antibody (MAb) CC49 was modified by engineering DNA coding sequences to lower its isoelectric point. Negatively charged amino acids were added to the carboxy terminus of the CC49 V
H region by adding nucleotide sequences in a polymerase chain reaction (PCR) amplification of the coding sequence of CC49 scFv. Two new DNA constructs coding for CC49 scFv with lower isoelectric points of 5.8 and 5.2 were engineered. These novel strategy-generated, charge-modified antibody constructs were compared for their immunological, pharmacokinetic, and biodistribution properties in athymic mice bearing LS-174T human colon carcinoma xenografts.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>10096498</pmid><doi>10.1016/S0969-8051(98)00075-4</doi><tpages>8</tpages></addata></record> |
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| ispartof | Nuclear medicine and biology, 1999, Vol.26 (1), p.27-34 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Amino Acid Sequence Animals Antibodies, Neoplasm - biosynthesis Antibodies, Neoplasm - metabolism Antibody engineering Antibody Formation Base Sequence Biological and medical sciences Carcinoma - metabolism Colon carcinoma xenografts Colonic Neoplasms - metabolism Digestive system Female Humans Immunoglobulin Variable Region Investigative techniques, diagnostic techniques (general aspects) Iodine Radioisotopes Isoelectric Point Medical sciences Mice Mice, Nude Molecular Sequence Data Neoplasm Transplantation Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Polymerase Chain Reaction Radioimmunodiagnosis Radiopharmaceuticals Single chain fragments |
| title | Charge-modified single chain antibody constructs of monoclonal antibody CC49: generation, characterization, pharmacokinetics, and biodistribution analysis |
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