Artificial capillary culture : expansion and retroviral transduction of CD4+ T-lymphocytes for clinical application
An artificial capillary culture/transduction technique has been developed for application in a phase I gene therapy clinical trial for HIV. The trial protocol involves isolation of CD4+ T-lymphocytes from a genetically matched HIV negative twin, retroviral transduction of equal numbers of cells with...
Gespeichert in:
| Veröffentlicht in: | Gene therapy 1999-03, Vol.6 (3), p.373-384 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 384 |
|---|---|
| container_issue | 3 |
| container_start_page | 373 |
| container_title | Gene therapy |
| container_volume | 6 |
| creator | KNOP, A. E ARNDT, A. J RAPONI, M BOYD, M. P ELY, J. A SYMONDS, G |
| description | An artificial capillary culture/transduction technique has been developed for application in a phase I gene therapy clinical trial for HIV. The trial protocol involves isolation of CD4+ T-lymphocytes from a genetically matched HIV negative twin, retroviral transduction of equal numbers of cells with the ribozyme therapeutic and control genes, and expansion in Cellmax artificial capillary modules. Preclinical studies showed transduction efficiencies in the range of 3-30%, with preferential expansion of CD4+ lymphocytes over a culture period of 10-14 days. Over this time period, an average yield of 1.7 x 10(9) lymphocytes was readily attainable from 5 x 10(7) CD8-depleted lymphocytes. In addition, a sensitive and reliable quantitative competitive PCR method was developed to assess the levels of transduction before infusion into the recipient. The transduction data suggest that the efficiency of retroviral transduction was affected by the presence of inhibitory factors present in the virus preparations or generated as a result of the transduction process itself. It is hypothesised that the method of transduction could significantly affect the extent of this inhibition, and thus impact on clinical efficacy of retrovirus mediated gene therapy. |
| doi_str_mv | 10.1038/sj.gt.3300822 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69935533</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>69935533</sourcerecordid><originalsourceid>FETCH-LOGICAL-c385t-5ebaba712369a6a9c224c72d6487661ad453c6404f22a6044b1133aa7f0b81e33</originalsourceid><addsrcrecordid>eNpd0c9LwzAUB_Agis4fR68SULxIZ341Tb2N-RMGXuY5pGmqGV1Tk1Tcf2_KBoqnhOTD473vA-AcoylGVNyG1fQ9TilFSBCyByaYFTzLGSf7YIJKXmYFJuIIHIewQgixQpBDcIQRozkSxQSEmY-2sdqqFmrV27ZVfgP10MbBG3gHzXevumBdB1VXQ2-id1_WJxx9eq8HHcc_18D5PbuBy6zdrPsPpzfRBNg4D3VrO6uTV33fpsvIT8FBo9pgznbnCXh7fFjOn7PF69PLfLbINBV5zHJTqUql9ikvFVelJoTpgtSciYJzrGqWU80ZYg0hiiPGKowpVapoUCWwofQEXG_r9t59DiZEubZBmzRiZ9wQJC9Lmud0hJf_4MoNvku9ScIZ45hgMapsq7R3IXjTyN7bdYpLYiTHXciwku9R7naR_MWu6lCtTf1Hb8NP4GoHVEgRNSlRbcOvKyjhlNMfWKqSKQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2644612183</pqid></control><display><type>article</type><title>Artificial capillary culture : expansion and retroviral transduction of CD4+ T-lymphocytes for clinical application</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>KNOP, A. E ; ARNDT, A. J ; RAPONI, M ; BOYD, M. P ; ELY, J. A ; SYMONDS, G</creator><creatorcontrib>KNOP, A. E ; ARNDT, A. J ; RAPONI, M ; BOYD, M. P ; ELY, J. A ; SYMONDS, G</creatorcontrib><description>An artificial capillary culture/transduction technique has been developed for application in a phase I gene therapy clinical trial for HIV. The trial protocol involves isolation of CD4+ T-lymphocytes from a genetically matched HIV negative twin, retroviral transduction of equal numbers of cells with the ribozyme therapeutic and control genes, and expansion in Cellmax artificial capillary modules. Preclinical studies showed transduction efficiencies in the range of 3-30%, with preferential expansion of CD4+ lymphocytes over a culture period of 10-14 days. Over this time period, an average yield of 1.7 x 10(9) lymphocytes was readily attainable from 5 x 10(7) CD8-depleted lymphocytes. In addition, a sensitive and reliable quantitative competitive PCR method was developed to assess the levels of transduction before infusion into the recipient. The transduction data suggest that the efficiency of retroviral transduction was affected by the presence of inhibitory factors present in the virus preparations or generated as a result of the transduction process itself. It is hypothesised that the method of transduction could significantly affect the extent of this inhibition, and thus impact on clinical efficacy of retrovirus mediated gene therapy.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/sj.gt.3300822</identifier><identifier>PMID: 10435087</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>AIDS/HIV ; Biological and medical sciences ; Biotechnology ; CD4 antigen ; CD4-Positive T-Lymphocytes ; CD8 antigen ; Cell culture ; Cell Culture Techniques ; Cells, Cultured ; Flow Cytometry ; Fundamental and applied biological sciences. Psychology ; Gene therapy ; Genetic Therapy - methods ; Genetic Vectors ; Health. Pharmaceutical industry ; HIV ; Human immunodeficiency virus ; Humans ; Industrial applications and implications. Economical aspects ; Lymphocytes ; Lymphocytes T ; Polymerase Chain Reaction - methods ; Retroviridae - genetics ; Transduction ; Transfection - methods</subject><ispartof>Gene therapy, 1999-03, Vol.6 (3), p.373-384</ispartof><rights>1999 INIST-CNRS</rights><rights>Macmillan Publishers Limited 1999.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-5ebaba712369a6a9c224c72d6487661ad453c6404f22a6044b1133aa7f0b81e33</citedby><cites>FETCH-LOGICAL-c385t-5ebaba712369a6a9c224c72d6487661ad453c6404f22a6044b1133aa7f0b81e33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1732636$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10435087$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KNOP, A. E</creatorcontrib><creatorcontrib>ARNDT, A. J</creatorcontrib><creatorcontrib>RAPONI, M</creatorcontrib><creatorcontrib>BOYD, M. P</creatorcontrib><creatorcontrib>ELY, J. A</creatorcontrib><creatorcontrib>SYMONDS, G</creatorcontrib><title>Artificial capillary culture : expansion and retroviral transduction of CD4+ T-lymphocytes for clinical application</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><description>An artificial capillary culture/transduction technique has been developed for application in a phase I gene therapy clinical trial for HIV. The trial protocol involves isolation of CD4+ T-lymphocytes from a genetically matched HIV negative twin, retroviral transduction of equal numbers of cells with the ribozyme therapeutic and control genes, and expansion in Cellmax artificial capillary modules. Preclinical studies showed transduction efficiencies in the range of 3-30%, with preferential expansion of CD4+ lymphocytes over a culture period of 10-14 days. Over this time period, an average yield of 1.7 x 10(9) lymphocytes was readily attainable from 5 x 10(7) CD8-depleted lymphocytes. In addition, a sensitive and reliable quantitative competitive PCR method was developed to assess the levels of transduction before infusion into the recipient. The transduction data suggest that the efficiency of retroviral transduction was affected by the presence of inhibitory factors present in the virus preparations or generated as a result of the transduction process itself. It is hypothesised that the method of transduction could significantly affect the extent of this inhibition, and thus impact on clinical efficacy of retrovirus mediated gene therapy.</description><subject>AIDS/HIV</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes</subject><subject>CD8 antigen</subject><subject>Cell culture</subject><subject>Cell Culture Techniques</subject><subject>Cells, Cultured</subject><subject>Flow Cytometry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene therapy</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Health. Pharmaceutical industry</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Retroviridae - genetics</subject><subject>Transduction</subject><subject>Transfection - methods</subject><issn>0969-7128</issn><issn>1476-5462</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0c9LwzAUB_Agis4fR68SULxIZ341Tb2N-RMGXuY5pGmqGV1Tk1Tcf2_KBoqnhOTD473vA-AcoylGVNyG1fQ9TilFSBCyByaYFTzLGSf7YIJKXmYFJuIIHIewQgixQpBDcIQRozkSxQSEmY-2sdqqFmrV27ZVfgP10MbBG3gHzXevumBdB1VXQ2-id1_WJxx9eq8HHcc_18D5PbuBy6zdrPsPpzfRBNg4D3VrO6uTV33fpsvIT8FBo9pgznbnCXh7fFjOn7PF69PLfLbINBV5zHJTqUql9ikvFVelJoTpgtSciYJzrGqWU80ZYg0hiiPGKowpVapoUCWwofQEXG_r9t59DiZEubZBmzRiZ9wQJC9Lmud0hJf_4MoNvku9ScIZ45hgMapsq7R3IXjTyN7bdYpLYiTHXciwku9R7naR_MWu6lCtTf1Hb8NP4GoHVEgRNSlRbcOvKyjhlNMfWKqSKQ</recordid><startdate>19990301</startdate><enddate>19990301</enddate><creator>KNOP, A. E</creator><creator>ARNDT, A. J</creator><creator>RAPONI, M</creator><creator>BOYD, M. P</creator><creator>ELY, J. A</creator><creator>SYMONDS, G</creator><general>Nature Publishing Group</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>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19990301</creationdate><title>Artificial capillary culture : expansion and retroviral transduction of CD4+ T-lymphocytes for clinical application</title><author>KNOP, A. E ; ARNDT, A. J ; RAPONI, M ; BOYD, M. P ; ELY, J. A ; SYMONDS, G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-5ebaba712369a6a9c224c72d6487661ad453c6404f22a6044b1133aa7f0b81e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>AIDS/HIV</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes</topic><topic>CD8 antigen</topic><topic>Cell culture</topic><topic>Cell Culture Techniques</topic><topic>Cells, Cultured</topic><topic>Flow Cytometry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene therapy</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors</topic><topic>Health. Pharmaceutical industry</topic><topic>HIV</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Polymerase Chain Reaction - methods</topic><topic>Retroviridae - genetics</topic><topic>Transduction</topic><topic>Transfection - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KNOP, A. E</creatorcontrib><creatorcontrib>ARNDT, A. J</creatorcontrib><creatorcontrib>RAPONI, M</creatorcontrib><creatorcontrib>BOYD, M. P</creatorcontrib><creatorcontrib>ELY, J. A</creatorcontrib><creatorcontrib>SYMONDS, G</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>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KNOP, A. E</au><au>ARNDT, A. J</au><au>RAPONI, M</au><au>BOYD, M. P</au><au>ELY, J. A</au><au>SYMONDS, G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Artificial capillary culture : expansion and retroviral transduction of CD4+ T-lymphocytes for clinical application</atitle><jtitle>Gene therapy</jtitle><addtitle>Gene Ther</addtitle><date>1999-03-01</date><risdate>1999</risdate><volume>6</volume><issue>3</issue><spage>373</spage><epage>384</epage><pages>373-384</pages><issn>0969-7128</issn><eissn>1476-5462</eissn><abstract>An artificial capillary culture/transduction technique has been developed for application in a phase I gene therapy clinical trial for HIV. The trial protocol involves isolation of CD4+ T-lymphocytes from a genetically matched HIV negative twin, retroviral transduction of equal numbers of cells with the ribozyme therapeutic and control genes, and expansion in Cellmax artificial capillary modules. Preclinical studies showed transduction efficiencies in the range of 3-30%, with preferential expansion of CD4+ lymphocytes over a culture period of 10-14 days. Over this time period, an average yield of 1.7 x 10(9) lymphocytes was readily attainable from 5 x 10(7) CD8-depleted lymphocytes. In addition, a sensitive and reliable quantitative competitive PCR method was developed to assess the levels of transduction before infusion into the recipient. The transduction data suggest that the efficiency of retroviral transduction was affected by the presence of inhibitory factors present in the virus preparations or generated as a result of the transduction process itself. It is hypothesised that the method of transduction could significantly affect the extent of this inhibition, and thus impact on clinical efficacy of retrovirus mediated gene therapy.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>10435087</pmid><doi>10.1038/sj.gt.3300822</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0969-7128 |
| ispartof | Gene therapy, 1999-03, Vol.6 (3), p.373-384 |
| issn | 0969-7128 1476-5462 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69935533 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | AIDS/HIV Biological and medical sciences Biotechnology CD4 antigen CD4-Positive T-Lymphocytes CD8 antigen Cell culture Cell Culture Techniques Cells, Cultured Flow Cytometry Fundamental and applied biological sciences. Psychology Gene therapy Genetic Therapy - methods Genetic Vectors Health. Pharmaceutical industry HIV Human immunodeficiency virus Humans Industrial applications and implications. Economical aspects Lymphocytes Lymphocytes T Polymerase Chain Reaction - methods Retroviridae - genetics Transduction Transfection - methods |
| title | Artificial capillary culture : expansion and retroviral transduction of CD4+ T-lymphocytes for clinical application |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T19%3A51%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Artificial%20capillary%20culture%20:%20expansion%20and%20retroviral%20transduction%20of%20CD4+%20T-lymphocytes%20for%20clinical%20application&rft.jtitle=Gene%20therapy&rft.au=KNOP,%20A.%20E&rft.date=1999-03-01&rft.volume=6&rft.issue=3&rft.spage=373&rft.epage=384&rft.pages=373-384&rft.issn=0969-7128&rft.eissn=1476-5462&rft_id=info:doi/10.1038/sj.gt.3300822&rft_dat=%3Cproquest_cross%3E69935533%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2644612183&rft_id=info:pmid/10435087&rfr_iscdi=true |