Preparation of antigastric cancer monoclonal antibody MGb2-mitomycin C conjugate with improved antitumor activity
In the present study, an antigastric cancer monoclonal antibody, MGb2, was chosen to prepare antibody-mitomycin C conjugate with dextran T-40 as intermediary. Up to 20 molecules of mitomycin C were specifically bound per molecule of antibody, without significantly impairing the antigen-binding capac...
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| Veröffentlicht in: | Bioconjugate chemistry 1990-07, Vol.1 (4), p.245-250 |
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| container_title | Bioconjugate chemistry |
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| creator | Li, Song Zhang, Xueyong Zhang, Suyin Chen, Xitao Chen, Lingji Shu, Yuhua Zhang, Jialiu Fan, Daiming |
| description | In the present study, an antigastric cancer monoclonal antibody, MGb2, was chosen to prepare antibody-mitomycin C conjugate with dextran T-40 as intermediary. Up to 20 molecules of mitomycin C were specifically bound per molecule of antibody, without significantly impairing the antigen-binding capacity of the antibody and the pharmacological activity of mitomycin C. The conjugate showed selective cytotoxicity upon human gastric cancer cell line SGC-7901 in vitro. Radioimmunoimaging and biodistribution studies indicated that, after conjugation with mitomycin C via dextran T-40 as intermediary, the tumor localization capacity of the antibody was well-retained. When tested in nude mice inoculated with human gastric carcinoma GAII in bilateral subrenal capsules, intraperitoneal injection of the conjugate twice a week for 3 weeks at the dose of 1 mg/kg of drug gave a tumor inhibitory rate of 152.29%, the result being far better than that of free mitomycin C or an irrelevant conjugate. A similar result was found in another nude mouse model of human gastric carcinoma SGC-7901. Meanwhile, after conjugation with antibody, the toxicity of mitomycin C on tested animals was significantly reduced. |
| doi_str_mv | 10.1021/bc00004a003 |
| format | Article |
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Up to 20 molecules of mitomycin C were specifically bound per molecule of antibody, without significantly impairing the antigen-binding capacity of the antibody and the pharmacological activity of mitomycin C. The conjugate showed selective cytotoxicity upon human gastric cancer cell line SGC-7901 in vitro. Radioimmunoimaging and biodistribution studies indicated that, after conjugation with mitomycin C via dextran T-40 as intermediary, the tumor localization capacity of the antibody was well-retained. When tested in nude mice inoculated with human gastric carcinoma GAII in bilateral subrenal capsules, intraperitoneal injection of the conjugate twice a week for 3 weeks at the dose of 1 mg/kg of drug gave a tumor inhibitory rate of 152.29%, the result being far better than that of free mitomycin C or an irrelevant conjugate. A similar result was found in another nude mouse model of human gastric carcinoma SGC-7901. Meanwhile, after conjugation with antibody, the toxicity of mitomycin C on tested animals was significantly reduced.</description><identifier>ISSN: 1043-1802</identifier><identifier>EISSN: 1520-4812</identifier><identifier>DOI: 10.1021/bc00004a003</identifier><identifier>PMID: 2129014</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - pharmacology ; Antineoplastic Agents - pharmacology ; Cell Survival - drug effects ; Drug Stability ; Humans ; Immunotoxins - chemical synthesis ; Immunotoxins - pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred Strains ; Mice, Nude ; Mitomycin ; Mitomycins - pharmacology ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - immunology ; Stomach Neoplasms - pathology ; Transplantation, Heterologous ; Tumor Cells, Cultured</subject><ispartof>Bioconjugate chemistry, 1990-07, Vol.1 (4), p.245-250</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a269t-25cd1897910259f88a62f28c23230a9edcda9c7f01f703f605cf7a8b4e194843</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bc00004a003$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bc00004a003$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2129014$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Song</creatorcontrib><creatorcontrib>Zhang, Xueyong</creatorcontrib><creatorcontrib>Zhang, Suyin</creatorcontrib><creatorcontrib>Chen, Xitao</creatorcontrib><creatorcontrib>Chen, Lingji</creatorcontrib><creatorcontrib>Shu, Yuhua</creatorcontrib><creatorcontrib>Zhang, Jialiu</creatorcontrib><creatorcontrib>Fan, Daiming</creatorcontrib><title>Preparation of antigastric cancer monoclonal antibody MGb2-mitomycin C conjugate with improved antitumor activity</title><title>Bioconjugate chemistry</title><addtitle>Bioconjugate Chem</addtitle><description>In the present study, an antigastric cancer monoclonal antibody, MGb2, was chosen to prepare antibody-mitomycin C conjugate with dextran T-40 as intermediary. Up to 20 molecules of mitomycin C were specifically bound per molecule of antibody, without significantly impairing the antigen-binding capacity of the antibody and the pharmacological activity of mitomycin C. The conjugate showed selective cytotoxicity upon human gastric cancer cell line SGC-7901 in vitro. Radioimmunoimaging and biodistribution studies indicated that, after conjugation with mitomycin C via dextran T-40 as intermediary, the tumor localization capacity of the antibody was well-retained. When tested in nude mice inoculated with human gastric carcinoma GAII in bilateral subrenal capsules, intraperitoneal injection of the conjugate twice a week for 3 weeks at the dose of 1 mg/kg of drug gave a tumor inhibitory rate of 152.29%, the result being far better than that of free mitomycin C or an irrelevant conjugate. A similar result was found in another nude mouse model of human gastric carcinoma SGC-7901. Meanwhile, after conjugation with antibody, the toxicity of mitomycin C on tested animals was significantly reduced.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Cell Survival - drug effects</subject><subject>Drug Stability</subject><subject>Humans</subject><subject>Immunotoxins - chemical synthesis</subject><subject>Immunotoxins - pharmacology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred Strains</subject><subject>Mice, Nude</subject><subject>Mitomycin</subject><subject>Mitomycins - pharmacology</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach Neoplasms - immunology</subject><subject>Stomach Neoplasms - pathology</subject><subject>Transplantation, Heterologous</subject><subject>Tumor Cells, Cultured</subject><issn>1043-1802</issn><issn>1520-4812</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkEFPAjEQRhujQUVPnk1682BW2-4u2x6VKBgxksi9me22WGS32BaUf-8KhHiwl2nyvZnJPIQuKLmhhNHbUpH2ZUBIeoBOaM5IknHKDts_ydKEcsKO0WkIs5YSlLMO6jDKBKHZCfoce70AD9G6BjuDoYl2CiF6q7CCRmmPa9c4NXcNzDdp6ao1fhmULKltdPVa2Qb3sXLNbDmFqPGXje_Y1gvvVrradMRl7TwGFe3KxvUZOjIwD_p8V7to8vgw6Q-T0evgqX83SoD1RExYrirKRSHaE3NhOIceM4wrlrKUgNCVqkCowhBqCpKaHsmVKYCXmaYi41naRdfbscq7ELw2cuFtDX4tKZG_2uQfbS19uaUXy7LW1Z7deWrzZJvbEPX3Pgb_IXtFWuRyMn6T4pmOxvdDJkXLX215UEHO3NK39sK_m38AkkOEzA</recordid><startdate>19900701</startdate><enddate>19900701</enddate><creator>Li, Song</creator><creator>Zhang, Xueyong</creator><creator>Zhang, Suyin</creator><creator>Chen, Xitao</creator><creator>Chen, Lingji</creator><creator>Shu, Yuhua</creator><creator>Zhang, Jialiu</creator><creator>Fan, Daiming</creator><general>American Chemical Society</general><scope>BSCLL</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></search><sort><creationdate>19900701</creationdate><title>Preparation of antigastric cancer monoclonal antibody MGb2-mitomycin C conjugate with improved antitumor activity</title><author>Li, Song ; Zhang, Xueyong ; Zhang, Suyin ; Chen, Xitao ; Chen, Lingji ; Shu, Yuhua ; Zhang, Jialiu ; Fan, Daiming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a269t-25cd1897910259f88a62f28c23230a9edcda9c7f01f703f605cf7a8b4e194843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Cell Survival - drug effects</topic><topic>Drug Stability</topic><topic>Humans</topic><topic>Immunotoxins - chemical synthesis</topic><topic>Immunotoxins - pharmacology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred Strains</topic><topic>Mice, Nude</topic><topic>Mitomycin</topic><topic>Mitomycins - pharmacology</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Stomach Neoplasms - immunology</topic><topic>Stomach Neoplasms - pathology</topic><topic>Transplantation, Heterologous</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Song</creatorcontrib><creatorcontrib>Zhang, Xueyong</creatorcontrib><creatorcontrib>Zhang, Suyin</creatorcontrib><creatorcontrib>Chen, Xitao</creatorcontrib><creatorcontrib>Chen, Lingji</creatorcontrib><creatorcontrib>Shu, Yuhua</creatorcontrib><creatorcontrib>Zhang, Jialiu</creatorcontrib><creatorcontrib>Fan, Daiming</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Bioconjugate chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Song</au><au>Zhang, Xueyong</au><au>Zhang, Suyin</au><au>Chen, Xitao</au><au>Chen, Lingji</au><au>Shu, Yuhua</au><au>Zhang, Jialiu</au><au>Fan, Daiming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preparation of antigastric cancer monoclonal antibody MGb2-mitomycin C conjugate with improved antitumor activity</atitle><jtitle>Bioconjugate chemistry</jtitle><addtitle>Bioconjugate Chem</addtitle><date>1990-07-01</date><risdate>1990</risdate><volume>1</volume><issue>4</issue><spage>245</spage><epage>250</epage><pages>245-250</pages><issn>1043-1802</issn><eissn>1520-4812</eissn><abstract>In the present study, an antigastric cancer monoclonal antibody, MGb2, was chosen to prepare antibody-mitomycin C conjugate with dextran T-40 as intermediary. Up to 20 molecules of mitomycin C were specifically bound per molecule of antibody, without significantly impairing the antigen-binding capacity of the antibody and the pharmacological activity of mitomycin C. The conjugate showed selective cytotoxicity upon human gastric cancer cell line SGC-7901 in vitro. Radioimmunoimaging and biodistribution studies indicated that, after conjugation with mitomycin C via dextran T-40 as intermediary, the tumor localization capacity of the antibody was well-retained. When tested in nude mice inoculated with human gastric carcinoma GAII in bilateral subrenal capsules, intraperitoneal injection of the conjugate twice a week for 3 weeks at the dose of 1 mg/kg of drug gave a tumor inhibitory rate of 152.29%, the result being far better than that of free mitomycin C or an irrelevant conjugate. A similar result was found in another nude mouse model of human gastric carcinoma SGC-7901. Meanwhile, after conjugation with antibody, the toxicity of mitomycin C on tested animals was significantly reduced.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>2129014</pmid><doi>10.1021/bc00004a003</doi><tpages>6</tpages></addata></record> |
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| identifier | ISSN: 1043-1802 |
| ispartof | Bioconjugate chemistry, 1990-07, Vol.1 (4), p.245-250 |
| issn | 1043-1802 1520-4812 |
| language | eng |
| recordid | cdi_crossref_primary_10_1021_bc00004a003 |
| source | MEDLINE; American Chemical Society Journals |
| subjects | Animals Antibodies, Monoclonal - immunology Antibodies, Monoclonal - pharmacology Antineoplastic Agents - pharmacology Cell Survival - drug effects Drug Stability Humans Immunotoxins - chemical synthesis Immunotoxins - pharmacology Mice Mice, Inbred BALB C Mice, Inbred Strains Mice, Nude Mitomycin Mitomycins - pharmacology Stomach Neoplasms - drug therapy Stomach Neoplasms - immunology Stomach Neoplasms - pathology Transplantation, Heterologous Tumor Cells, Cultured |
| title | Preparation of antigastric cancer monoclonal antibody MGb2-mitomycin C conjugate with improved antitumor activity |
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