Trichosanthin-monoclonal antibody conjugate specifically cytotoxic to human hepatoma cells in vitro
A plant single-chain ribosome-inactivating protein derived from the root tuber of Trichosanthes kirilowii, termed trichosanthin (TCS), was modified with 2-iminothiolane. It was not like trichokirin, a ribosome-inactivating protein derived from the seeds of the same plant, in that TCS retained full a...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 1991-07, Vol.51 (13), p.3353-3355 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | Wang, Q C Ying, W B Xie, H Zhang, Z C Yang, Z H Ling, L Q |
| description | A plant single-chain ribosome-inactivating protein derived from the root tuber of Trichosanthes kirilowii, termed trichosanthin (TCS), was modified with 2-iminothiolane. It was not like trichokirin, a ribosome-inactivating protein derived from the seeds of the same plant, in that TCS retained full activity when 1.5 sulfhydryl groups were introduced into each TCS molecule by 2-iminothiolane modification. The 2-iminothiolane-TCS was conjugated to Hepama-1, a monoclonal antibody directed against human hepatoma with a cross-linking reagent, N-succinimidyl-3-(2-pyridyl)-dithiopropionate. The hepatoma cytotoxicity of the immunotoxin, TCS-Hepama-1, was 500-fold higher than that of free TCS and only 1 log lower than that of free ricin. However, the immunotoxin was approximately 600-fold less cytotoxic to HeLa cells. The results suggested that the immunotoxin was a potent and quite specific antihepatoma agent and might have considerable potential in hepatoma therapy. |
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It was not like trichokirin, a ribosome-inactivating protein derived from the seeds of the same plant, in that TCS retained full activity when 1.5 sulfhydryl groups were introduced into each TCS molecule by 2-iminothiolane modification. The 2-iminothiolane-TCS was conjugated to Hepama-1, a monoclonal antibody directed against human hepatoma with a cross-linking reagent, N-succinimidyl-3-(2-pyridyl)-dithiopropionate. The hepatoma cytotoxicity of the immunotoxin, TCS-Hepama-1, was 500-fold higher than that of free TCS and only 1 log lower than that of free ricin. However, the immunotoxin was approximately 600-fold less cytotoxic to HeLa cells. The results suggested that the immunotoxin was a potent and quite specific antihepatoma agent and might have considerable potential in hepatoma therapy.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 1647265</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Antibodies, Monoclonal - chemistry ; Antibodies, Monoclonal - therapeutic use ; Antineoplastic agents ; Biological and medical sciences ; Carcinoma, Hepatocellular - therapy ; Cell Survival - drug effects ; General aspects ; Humans ; Immunotoxins - toxicity ; In Vitro Techniques ; Liver Neoplasms - therapy ; Medical sciences ; Pharmacology. Drug treatments ; Protein Biosynthesis ; Trichosanthin - administration & dosage ; Tumor Cells, Cultured</subject><ispartof>Cancer research (Chicago, Ill.), 1991-07, Vol.51 (13), p.3353-3355</ispartof><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19819614$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1647265$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Q C</creatorcontrib><creatorcontrib>Ying, W B</creatorcontrib><creatorcontrib>Xie, H</creatorcontrib><creatorcontrib>Zhang, Z C</creatorcontrib><creatorcontrib>Yang, Z H</creatorcontrib><creatorcontrib>Ling, L Q</creatorcontrib><title>Trichosanthin-monoclonal antibody conjugate specifically cytotoxic to human hepatoma cells in vitro</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>A plant single-chain ribosome-inactivating protein derived from the root tuber of Trichosanthes kirilowii, termed trichosanthin (TCS), was modified with 2-iminothiolane. It was not like trichokirin, a ribosome-inactivating protein derived from the seeds of the same plant, in that TCS retained full activity when 1.5 sulfhydryl groups were introduced into each TCS molecule by 2-iminothiolane modification. The 2-iminothiolane-TCS was conjugated to Hepama-1, a monoclonal antibody directed against human hepatoma with a cross-linking reagent, N-succinimidyl-3-(2-pyridyl)-dithiopropionate. The hepatoma cytotoxicity of the immunotoxin, TCS-Hepama-1, was 500-fold higher than that of free TCS and only 1 log lower than that of free ricin. However, the immunotoxin was approximately 600-fold less cytotoxic to HeLa cells. The results suggested that the immunotoxin was a potent and quite specific antihepatoma agent and might have considerable potential in hepatoma therapy.</description><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - therapy</subject><subject>Cell Survival - drug effects</subject><subject>General aspects</subject><subject>Humans</subject><subject>Immunotoxins - toxicity</subject><subject>In Vitro Techniques</subject><subject>Liver Neoplasms - therapy</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Biosynthesis</subject><subject>Trichosanthin - administration & dosage</subject><subject>Tumor Cells, Cultured</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFj01LxDAYhIMo67r6E4RcPBaSpvnoURa_YMHLel7S5K3NkialScX-ewsW9jTMM8PAXKEt5UwVsqr4NdoSQlTBK1neoruUzovllPAN2lCxQMG3yBxHZ7qYdMidC0UfQzQ-Bu3xQlwT7YxNDOfpW2fAaQDjWme09wuec8zx1xmcI-6mXgfcwaBz7DU24H3CLuAfl8d4j25a7RM8rLpDX68vx_17cfh8-9g_H4qOKp4LxVvTWMla4NKCKIEAq5lghFWa2qYkRJZEMSmNKilwWxmiQNUgSy4UtYLt0OP_7jA1PdjTMLpej_NpPbvkT2uu0_KhHXUwLl1qtaK1oBX7AwDPYBU</recordid><startdate>19910701</startdate><enddate>19910701</enddate><creator>Wang, Q C</creator><creator>Ying, W B</creator><creator>Xie, H</creator><creator>Zhang, Z C</creator><creator>Yang, Z H</creator><creator>Ling, L Q</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>19910701</creationdate><title>Trichosanthin-monoclonal antibody conjugate specifically cytotoxic to human hepatoma cells in vitro</title><author>Wang, Q C ; Ying, W B ; Xie, H ; Zhang, Z C ; Yang, Z H ; Ling, L Q</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h185t-85fcbd73fe57de62e0e39363034a1db2007208377c821e5d4c08e89e725681d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Antibodies, Monoclonal - chemistry</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - therapy</topic><topic>Cell Survival - drug effects</topic><topic>General aspects</topic><topic>Humans</topic><topic>Immunotoxins - toxicity</topic><topic>In Vitro Techniques</topic><topic>Liver Neoplasms - therapy</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Biosynthesis</topic><topic>Trichosanthin - administration & dosage</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Q C</creatorcontrib><creatorcontrib>Ying, W B</creatorcontrib><creatorcontrib>Xie, H</creatorcontrib><creatorcontrib>Zhang, Z C</creatorcontrib><creatorcontrib>Yang, Z H</creatorcontrib><creatorcontrib>Ling, L Q</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Q C</au><au>Ying, W B</au><au>Xie, H</au><au>Zhang, Z C</au><au>Yang, Z H</au><au>Ling, L Q</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trichosanthin-monoclonal antibody conjugate specifically cytotoxic to human hepatoma cells in vitro</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>1991-07-01</date><risdate>1991</risdate><volume>51</volume><issue>13</issue><spage>3353</spage><epage>3355</epage><pages>3353-3355</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>A plant single-chain ribosome-inactivating protein derived from the root tuber of Trichosanthes kirilowii, termed trichosanthin (TCS), was modified with 2-iminothiolane. It was not like trichokirin, a ribosome-inactivating protein derived from the seeds of the same plant, in that TCS retained full activity when 1.5 sulfhydryl groups were introduced into each TCS molecule by 2-iminothiolane modification. The 2-iminothiolane-TCS was conjugated to Hepama-1, a monoclonal antibody directed against human hepatoma with a cross-linking reagent, N-succinimidyl-3-(2-pyridyl)-dithiopropionate. The hepatoma cytotoxicity of the immunotoxin, TCS-Hepama-1, was 500-fold higher than that of free TCS and only 1 log lower than that of free ricin. However, the immunotoxin was approximately 600-fold less cytotoxic to HeLa cells. The results suggested that the immunotoxin was a potent and quite specific antihepatoma agent and might have considerable potential in hepatoma therapy.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>1647265</pmid><tpages>3</tpages></addata></record> |
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| ispartof | Cancer research (Chicago, Ill.), 1991-07, Vol.51 (13), p.3353-3355 |
| issn | 0008-5472 1538-7445 |
| language | eng |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| subjects | Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - therapeutic use Antineoplastic agents Biological and medical sciences Carcinoma, Hepatocellular - therapy Cell Survival - drug effects General aspects Humans Immunotoxins - toxicity In Vitro Techniques Liver Neoplasms - therapy Medical sciences Pharmacology. Drug treatments Protein Biosynthesis Trichosanthin - administration & dosage Tumor Cells, Cultured |
| title | Trichosanthin-monoclonal antibody conjugate specifically cytotoxic to human hepatoma cells in vitro |
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