Increased proliferation, lytic activity, and purity of human natural killer cells cocultured with mitogen-activated feeder cells
Identifieur interne : 001A12 ( Istex/Corpus ); précédent : 001A11; suivant : 001A13Increased proliferation, lytic activity, and purity of human natural killer cells cocultured with mitogen-activated feeder cells
Auteurs : Hannah Rabinowich ; Peter Sedlmayr ; Ronald B. Herberman ; Theresa L. WhitesideSource :
- Cellular Immunology [ 0008-8749 ] ; 1991.
English descriptors
- KwdEn :
- Activator, Adherent cells, Allogeneic, Cell, Cell cultures, Cell lines, Cell preparations, Cell proliferation, Cells cocultured, Cetus, Cocultured, Control cultures, Cytolytic, Cytolytic activity, Cytometry, Cytotoxicity, Daudi, Effector, Effector cells, Feeder, Feeder cells, Flow cytometry, Growth factors, Herberman, Immunol, Ionomycin, Lymphoblastoid, Lymphoblastoid cell lines, Lymphocyte, Magnetic beads, Monoclonal, Monoclonal antibodies, Normal donors, Okt3, Peripheral blood, Phenotype, Plastic surfaces, Positive selection, Preferential proliferation, Prestimulated, Proliferation, Rabinowich, Rubber policeman, Sufficient numbers, Target cells, Various combinations, Whiteside.
- Teeft :
- Activator, Adherent cells, Allogeneic, Cell, Cell cultures, Cell lines, Cell preparations, Cell proliferation, Cells cocultured, Cetus, Cocultured, Control cultures, Cytolytic, Cytolytic activity, Cytometry, Cytotoxicity, Daudi, Effector, Effector cells, Feeder, Feeder cells, Flow cytometry, Growth factors, Herberman, Immunol, Ionomycin, Lymphoblastoid, Lymphoblastoid cell lines, Lymphocyte, Magnetic beads, Monoclonal, Monoclonal antibodies, Normal donors, Okt3, Peripheral blood, Phenotype, Plastic surfaces, Positive selection, Preferential proliferation, Prestimulated, Proliferation, Rabinowich, Rubber policeman, Sufficient numbers, Target cells, Various combinations, Whiteside.
Abstract
Abstract: The addition of mitogen-prestimulated periferal blood lymphocytes (PBL) or Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) cultures to enriched populations of natural killer (NK) cells obtained from PBL of normal donors in the presence of rIL-2 resulted in highly significant increases in proliferation, purity, and cytolytic activity of cultured NK cells. Two sources of enriched NK cell preparations were used: (i) Adherent-lymphokine activated killer (A-LAK) cells obtained by adherence to plastic during 24 hr activation with 103 Cetus U/ml rIL-2; and (ii) NK cells negatively selected from PBL by removal of high-affinity rosette-forming cells and CD3+ lymphocytes. Coculture of A-LAK cells for 14 days with autologous or allogeneic Con A-activated PBL (106 cells/ml) or selected EBV-transformed LCL (2 × 105 cells/ml) as feeder cells increased fold expansion by a mean ± SEM of 629 fold ± 275 (P < 0.019) and 267 fold ± 54 (P < 0.0001), respectively, compared to 55 ± 20 in A-LAK cultures without feeder cells. The addition of either activated PBL or EBV lines to A-LAK cultures also led to a significant increase in the percentage of NK cells (CD3−CD56+) (84 ± 2.4 and 84 ± 2.6%, respectively, P < 0.0001 for both), compared to 53 ± 7.2% in cultures without feeders. The presence of feeder cells in cultures of A-LAK cells also led to significantly higher anti-tumor cytolytic activity compared to control cultures, as measured against NK-sensitive (K562) and NK-resistant (Daudi) target cells. Mitogen-stimulated CD4+ PBL purified by positive selection on antibody-coated flasks were better feeders than CD8+ or unseparated PBL. In the presence of feeder cells, it was possible to generate up to 6 × 109 activated NK cells from 2 × 108 fresh PBL by Day 13 of culture. Enhanced NK cell proliferation in the presence of feeder cells was not attributable to a detectable soluble factor. The improved method for generating A-LAK or activated-NK cells should facilitate cellular adoptive immunotherapy by providing sufficient numbers of highly enriched CD3−CD56+ effector cells with high anti-tumor activity.
Url:
DOI: 10.1016/0008-8749(91)90290-R
Links to Exploration step
ISTEX:717D4E17A0EA0E90EB8781587F92FBEC84499DCALe document en format XML
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Herberman</name><affiliation><mods:affiliation>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</mods:affiliation></affiliation></author><author><name sortKey="Whiteside, Theresa L" sort="Whiteside, Theresa L" uniqKey="Whiteside T" first="Theresa L." last="Whiteside">Theresa L. Whiteside</name><affiliation><mods:affiliation>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Cellular Immunology</title><title level="j" type="abbrev">YCIMM</title><idno type="ISSN">0008-8749</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1991">1991</date><biblScope unit="volume">135</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="454">454</biblScope><biblScope unit="page" to="470">470</biblScope></imprint><idno type="ISSN">0008-8749</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0008-8749</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Activator</term><term>Adherent cells</term><term>Allogeneic</term><term>Cell</term><term>Cell cultures</term><term>Cell lines</term><term>Cell preparations</term><term>Cell proliferation</term><term>Cells cocultured</term><term>Cetus</term><term>Cocultured</term><term>Control cultures</term><term>Cytolytic</term><term>Cytolytic activity</term><term>Cytometry</term><term>Cytotoxicity</term><term>Daudi</term><term>Effector</term><term>Effector cells</term><term>Feeder</term><term>Feeder cells</term><term>Flow cytometry</term><term>Growth factors</term><term>Herberman</term><term>Immunol</term><term>Ionomycin</term><term>Lymphoblastoid</term><term>Lymphoblastoid cell lines</term><term>Lymphocyte</term><term>Magnetic beads</term><term>Monoclonal</term><term>Monoclonal antibodies</term><term>Normal donors</term><term>Okt3</term><term>Peripheral blood</term><term>Phenotype</term><term>Plastic surfaces</term><term>Positive selection</term><term>Preferential proliferation</term><term>Prestimulated</term><term>Proliferation</term><term>Rabinowich</term><term>Rubber policeman</term><term>Sufficient numbers</term><term>Target cells</term><term>Various combinations</term><term>Whiteside</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Activator</term><term>Adherent cells</term><term>Allogeneic</term><term>Cell</term><term>Cell cultures</term><term>Cell lines</term><term>Cell preparations</term><term>Cell proliferation</term><term>Cells cocultured</term><term>Cetus</term><term>Cocultured</term><term>Control cultures</term><term>Cytolytic</term><term>Cytolytic activity</term><term>Cytometry</term><term>Cytotoxicity</term><term>Daudi</term><term>Effector</term><term>Effector cells</term><term>Feeder</term><term>Feeder cells</term><term>Flow cytometry</term><term>Growth factors</term><term>Herberman</term><term>Immunol</term><term>Ionomycin</term><term>Lymphoblastoid</term><term>Lymphoblastoid cell lines</term><term>Lymphocyte</term><term>Magnetic beads</term><term>Monoclonal</term><term>Monoclonal antibodies</term><term>Normal donors</term><term>Okt3</term><term>Peripheral blood</term><term>Phenotype</term><term>Plastic surfaces</term><term>Positive selection</term><term>Preferential proliferation</term><term>Prestimulated</term><term>Proliferation</term><term>Rabinowich</term><term>Rubber policeman</term><term>Sufficient numbers</term><term>Target cells</term><term>Various combinations</term><term>Whiteside</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The addition of mitogen-prestimulated periferal blood lymphocytes (PBL) or Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) cultures to enriched populations of natural killer (NK) cells obtained from PBL of normal donors in the presence of rIL-2 resulted in highly significant increases in proliferation, purity, and cytolytic activity of cultured NK cells. Two sources of enriched NK cell preparations were used: (i) Adherent-lymphokine activated killer (A-LAK) cells obtained by adherence to plastic during 24 hr activation with 103 Cetus U/ml rIL-2; and (ii) NK cells negatively selected from PBL by removal of high-affinity rosette-forming cells and CD3+ lymphocytes. Coculture of A-LAK cells for 14 days with autologous or allogeneic Con A-activated PBL (106 cells/ml) or selected EBV-transformed LCL (2 × 105 cells/ml) as feeder cells increased fold expansion by a mean ± SEM of 629 fold ± 275 (P < 0.019) and 267 fold ± 54 (P < 0.0001), respectively, compared to 55 ± 20 in A-LAK cultures without feeder cells. The addition of either activated PBL or EBV lines to A-LAK cultures also led to a significant increase in the percentage of NK cells (CD3−CD56+) (84 ± 2.4 and 84 ± 2.6%, respectively, P < 0.0001 for both), compared to 53 ± 7.2% in cultures without feeders. The presence of feeder cells in cultures of A-LAK cells also led to significantly higher anti-tumor cytolytic activity compared to control cultures, as measured against NK-sensitive (K562) and NK-resistant (Daudi) target cells. Mitogen-stimulated CD4+ PBL purified by positive selection on antibody-coated flasks were better feeders than CD8+ or unseparated PBL. In the presence of feeder cells, it was possible to generate up to 6 × 109 activated NK cells from 2 × 108 fresh PBL by Day 13 of culture. Enhanced NK cell proliferation in the presence of feeder cells was not attributable to a detectable soluble factor. The improved method for generating A-LAK or activated-NK cells should facilitate cellular adoptive immunotherapy by providing sufficient numbers of highly enriched CD3−CD56+ effector cells with high anti-tumor activity.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>feeder cells</json:string><json:string>lymphocyte</json:string><json:string>feeder</json:string><json:string>cocultured</json:string><json:string>okt3</json:string><json:string>cytolytic</json:string><json:string>daudi</json:string><json:string>immunol</json:string><json:string>cetus</json:string><json:string>cell cultures</json:string><json:string>herberman</json:string><json:string>cytotoxicity</json:string><json:string>allogeneic</json:string><json:string>cytolytic activity</json:string><json:string>effector</json:string><json:string>rabinowich</json:string><json:string>phenotype</json:string><json:string>lymphoblastoid</json:string><json:string>whiteside</json:string><json:string>cells cocultured</json:string><json:string>monoclonal</json:string><json:string>ionomycin</json:string><json:string>prestimulated</json:string><json:string>effector cells</json:string><json:string>activator</json:string><json:string>cell preparations</json:string><json:string>flow cytometry</json:string><json:string>cytometry</json:string><json:string>lymphoblastoid cell lines</json:string><json:string>proliferation</json:string><json:string>control cultures</json:string><json:string>cell lines</json:string><json:string>magnetic beads</json:string><json:string>monoclonal antibodies</json:string><json:string>peripheral blood</json:string><json:string>various combinations</json:string><json:string>preferential proliferation</json:string><json:string>growth factors</json:string><json:string>adherent cells</json:string><json:string>cell proliferation</json:string><json:string>positive selection</json:string><json:string>target cells</json:string><json:string>plastic surfaces</json:string><json:string>normal donors</json:string><json:string>rubber policeman</json:string><json:string>sufficient numbers</json:string><json:string>cell</json:string></teeft></keywords><author><json:item><name>Hannah Rabinowich</name><affiliations><json:string>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</json:string><json:string>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</json:string></affiliations></json:item><json:item><name>Peter Sedlmayr</name><affiliations><json:string>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</json:string><json:string>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</json:string></affiliations></json:item><json:item><name>Ronald B. Herberman</name><affiliations><json:string>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</json:string><json:string>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</json:string><json:string>Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</json:string></affiliations></json:item><json:item><name>Theresa L. Whiteside</name><affiliations><json:string>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</json:string><json:string>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</json:string></affiliations></json:item></author><articleId><json:string>9190290R</json:string></articleId><arkIstex>ark:/67375/6H6-35CGDHL7-5</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: The addition of mitogen-prestimulated periferal blood lymphocytes (PBL) or Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) cultures to enriched populations of natural killer (NK) cells obtained from PBL of normal donors in the presence of rIL-2 resulted in highly significant increases in proliferation, purity, and cytolytic activity of cultured NK cells. Two sources of enriched NK cell preparations were used: (i) Adherent-lymphokine activated killer (A-LAK) cells obtained by adherence to plastic during 24 hr activation with 103 Cetus U/ml rIL-2; and (ii) NK cells negatively selected from PBL by removal of high-affinity rosette-forming cells and CD3+ lymphocytes. Coculture of A-LAK cells for 14 days with autologous or allogeneic Con A-activated PBL (106 cells/ml) or selected EBV-transformed LCL (2 × 105 cells/ml) as feeder cells increased fold expansion by a mean ± SEM of 629 fold ± 275 (P > 0.019) and 267 fold ± 54 (P > 0.0001), respectively, compared to 55 ± 20 in A-LAK cultures without feeder cells. The addition of either activated PBL or EBV lines to A-LAK cultures also led to a significant increase in the percentage of NK cells (CD3−CD56+) (84 ± 2.4 and 84 ± 2.6%, respectively, P > 0.0001 for both), compared to 53 ± 7.2% in cultures without feeders. The presence of feeder cells in cultures of A-LAK cells also led to significantly higher anti-tumor cytolytic activity compared to control cultures, as measured against NK-sensitive (K562) and NK-resistant (Daudi) target cells. Mitogen-stimulated CD4+ PBL purified by positive selection on antibody-coated flasks were better feeders than CD8+ or unseparated PBL. In the presence of feeder cells, it was possible to generate up to 6 × 109 activated NK cells from 2 × 108 fresh PBL by Day 13 of culture. Enhanced NK cell proliferation in the presence of feeder cells was not attributable to a detectable soluble factor. The improved method for generating A-LAK or activated-NK cells should facilitate cellular adoptive immunotherapy by providing sufficient numbers of highly enriched CD3−CD56+ effector cells with high anti-tumor activity.</abstract><qualityIndicators><score>10</score><pdfWordCount>6565</pdfWordCount><pdfCharCount>39036</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>17</pdfPageCount><pdfPageSize>468 x 720 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>334</abstractWordCount><abstractCharCount>2142</abstractCharCount><keywordCount>0</keywordCount></qualityIndicators><title>Increased proliferation, lytic activity, and purity of human natural killer cells cocultured with mitogen-activated feeder cells</title><pmid><json:string>1709827</json:string></pmid><pii><json:string>0008-8749(91)90290-R</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>Cellular Immunology</title><language><json:string>unknown</json:string></language><publicationDate>1991</publicationDate><issn><json:string>0008-8749</json:string></issn><pii><json:string>S0008-8749(00)X0222-5</json:string></pii><volume>135</volume><issue>2</issue><pages><first>454</first><last>470</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>7258</json:string><json:string>1991</json:string><json:string>8037</json:string><json:string>4076</json:string></date><geogName></geogName><orgName><json:string>Becton-Dickinson</json:string><json:string>Calbiochem</json:string><json:string>Academic Press, Inc.</json:string><json:string>ACS Grant IM588A</json:string></orgName><orgName_funder><json:string>ACS Grant IM588A</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Perussia</json:string><json:string>Data</json:string><json:string>La Jolla</json:string><json:string>Thomas Okarma</json:string></persName><placeName><json:string>Cytotoxicity</json:string><json:string>San Diego</json:string><json:string>Grunwald</json:string><json:string>San Jose</json:string><json:string>Boston</json:string><json:string>CA</json:string><json:string>MA</json:string><json:string>Cambridge</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>Perussia et al.</json:string><json:string>Melder et al.</json:string><json:string>West et al.</json:string><json:string>Kobayashi et al.</json:string><json:string>Pross et al.</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-35CGDHL7-5</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - immunology</json:string><json:string>2 - cell biology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - clinical medicine</json:string><json:string>3 - immunology</json:string></scienceMetrix><scopus><json:string>1 - Life Sciences</json:string><json:string>2 - Immunology and Microbiology</json:string><json:string>3 - Immunology</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>1991</publicationDate><copyrightDate>1991</copyrightDate><doi><json:string>10.1016/0008-8749(91)90290-R</json:string></doi><id>717D4E17A0EA0E90EB8781587F92FBEC84499DCA</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/717D4E17A0EA0E90EB8781587F92FBEC84499DCA/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/717D4E17A0EA0E90EB8781587F92FBEC84499DCA/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/717D4E17A0EA0E90EB8781587F92FBEC84499DCA/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Increased proliferation, lytic activity, and purity of human natural killer cells cocultured with mitogen-activated feeder cells</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>1991</date></publicationStmt><notesStmt><note>This research was supported in part by ACS Grant IM588A to T.L.W.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Increased proliferation, lytic activity, and purity of human natural killer cells cocultured with mitogen-activated feeder cells</title><author xml:id="author-0000"><persName><forename type="first">Hannah</forename><surname>Rabinowich</surname></persName><affiliation>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><affiliation>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Peter</forename><surname>Sedlmayr</surname></persName><affiliation>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><affiliation>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Ronald B.</forename><surname>Herberman</surname></persName><affiliation>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><affiliation>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><affiliation>Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Theresa L.</forename><surname>Whiteside</surname></persName><affiliation>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><affiliation>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation></author><idno type="istex">717D4E17A0EA0E90EB8781587F92FBEC84499DCA</idno><idno type="DOI">10.1016/0008-8749(91)90290-R</idno><idno type="PII">0008-8749(91)90290-R</idno><idno type="ArticleID">9190290R</idno></analytic><monogr><title level="j">Cellular Immunology</title><title level="j" type="abbrev">YCIMM</title><idno type="pISSN">0008-8749</idno><idno type="PII">S0008-8749(00)X0222-5</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1991"></date><biblScope unit="volume">135</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="454">454</biblScope><biblScope unit="page" to="470">470</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1991</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The addition of mitogen-prestimulated periferal blood lymphocytes (PBL) or Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) cultures to enriched populations of natural killer (NK) cells obtained from PBL of normal donors in the presence of rIL-2 resulted in highly significant increases in proliferation, purity, and cytolytic activity of cultured NK cells. Two sources of enriched NK cell preparations were used: (i) Adherent-lymphokine activated killer (A-LAK) cells obtained by adherence to plastic during 24 hr activation with 103 Cetus U/ml rIL-2; and (ii) NK cells negatively selected from PBL by removal of high-affinity rosette-forming cells and CD3+ lymphocytes. Coculture of A-LAK cells for 14 days with autologous or allogeneic Con A-activated PBL (106 cells/ml) or selected EBV-transformed LCL (2 × 105 cells/ml) as feeder cells increased fold expansion by a mean ± SEM of 629 fold ± 275 (P < 0.019) and 267 fold ± 54 (P < 0.0001), respectively, compared to 55 ± 20 in A-LAK cultures without feeder cells. The addition of either activated PBL or EBV lines to A-LAK cultures also led to a significant increase in the percentage of NK cells (CD3−CD56+) (84 ± 2.4 and 84 ± 2.6%, respectively, P < 0.0001 for both), compared to 53 ± 7.2% in cultures without feeders. The presence of feeder cells in cultures of A-LAK cells also led to significantly higher anti-tumor cytolytic activity compared to control cultures, as measured against NK-sensitive (K562) and NK-resistant (Daudi) target cells. Mitogen-stimulated CD4+ PBL purified by positive selection on antibody-coated flasks were better feeders than CD8+ or unseparated PBL. In the presence of feeder cells, it was possible to generate up to 6 × 109 activated NK cells from 2 × 108 fresh PBL by Day 13 of culture. Enhanced NK cell proliferation in the presence of feeder cells was not attributable to a detectable soluble factor. The improved method for generating A-LAK or activated-NK cells should facilitate cellular adoptive immunotherapy by providing sufficient numbers of highly enriched CD3−CD56+ effector cells with high anti-tumor activity.</p></abstract></profileDesc><revisionDesc><change when="1991">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/717D4E17A0EA0E90EB8781587F92FBEC84499DCA/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: tail"><istex:xmlDeclaration>version="1.0" encoding="UTF-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla" xml:lang="en"><item-info><jid>YCIMM</jid><aid>9190290R</aid><ce:pii>0008-8749(91)90290-R</ce:pii><ce:doi>10.1016/0008-8749(91)90290-R</ce:doi><ce:copyright type="unknown" year="1991"></ce:copyright></item-info><head><ce:article-footnote><ce:label>☆</ce:label><ce:note-para>This research was supported in part by ACS Grant IM588A to T.L.W.</ce:note-para></ce:article-footnote><ce:title>Increased proliferation, lytic activity, and purity of human natural killer cells cocultured with mitogen-activated feeder cells</ce:title><ce:author-group><ce:author><ce:given-name>Hannah</ce:given-name><ce:surname>Rabinowich</ce:surname><ce:cross-ref refid="AFF1"><ce:sup loc="post">∗</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF2"><ce:sup loc="post">†</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Peter</ce:given-name><ce:surname>Sedlmayr</ce:surname><ce:cross-ref refid="AFF1"><ce:sup loc="post">∗</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF2"><ce:sup loc="post">†</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Ronald B.</ce:given-name><ce:surname>Herberman</ce:surname><ce:cross-ref refid="AFF1"><ce:sup loc="post">∗</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF2"><ce:sup loc="post">†</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF3"><ce:sup loc="post">‡</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Theresa L.</ce:given-name><ce:surname>Whiteside</ce:surname><ce:cross-ref refid="AFF1"><ce:sup loc="post">∗</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF2"><ce:sup loc="post">†</ce:sup></ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</ce:textfn></ce:affiliation></ce:author-group><ce:date-received day="1" month="11" year="1990"></ce:date-received><ce:date-accepted day="13" month="2" year="1991"></ce:date-accepted><ce:abstract class="author"><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para view="all" id="simple-para.0010">The addition of mitogen-prestimulated periferal blood lymphocytes (PBL) or Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) cultures to enriched populations of natural killer (NK) cells obtained from PBL of normal donors in the presence of rIL-2 resulted in highly significant increases in proliferation, purity, and cytolytic activity of cultured NK cells. Two sources of enriched NK cell preparations were used: (i) Adherent-lymphokine activated killer (A-LAK) cells obtained by adherence to plastic during 24 hr activation with 10<ce:sup loc="post">3</ce:sup> Cetus U/ml rIL-2; and (ii) NK cells negatively selected from PBL by removal of high-affinity rosette-forming cells and CD3<ce:sup loc="post">+</ce:sup> lymphocytes. Coculture of A-LAK cells for 14 days with autologous or allogeneic Con A-activated PBL (10<ce:sup loc="post">6</ce:sup> cells/ml) or selected EBV-transformed LCL (2 × 10<ce:sup loc="post">5</ce:sup> cells/ml) as feeder cells increased fold expansion by a mean ± SEM of 629 fold ± 275 (<ce:italic>P</ce:italic> < 0.019) and 267 fold ± 54 (<ce:italic>P</ce:italic> < 0.0001), respectively, compared to 55 ± 20 in A-LAK cultures without feeder cells. The addition of either activated PBL or EBV lines to A-LAK cultures also led to a significant increase in the percentage of NK cells (CD3<ce:sup loc="post">−</ce:sup>CD56<ce:sup loc="post">+</ce:sup>) (84 ± 2.4 and 84 ± 2.6%, respectively, <ce:italic>P</ce:italic> < 0.0001 for both), compared to 53 ± 7.2% in cultures without feeders. The presence of feeder cells in cultures of A-LAK cells also led to significantly higher anti-tumor cytolytic activity compared to control cultures, as measured against NK-sensitive (K562) and NK-resistant (Daudi) target cells. Mitogen-stimulated CD4<ce:sup loc="post">+</ce:sup> PBL purified by positive selection on antibody-coated flasks were better feeders than CD8<ce:sup loc="post">+</ce:sup> or unseparated PBL. In the presence of feeder cells, it was possible to generate up to 6 × 10<ce:sup loc="post">9</ce:sup> activated NK cells from 2 × 10<ce:sup loc="post">8</ce:sup> fresh PBL by Day 13 of culture. Enhanced NK cell proliferation in the presence of feeder cells was not attributable to a detectable soluble factor. The improved method for generating A-LAK or activated-NK cells should facilitate cellular adoptive immunotherapy by providing sufficient numbers of highly enriched CD3<ce:sup loc="post">−</ce:sup>CD56<ce:sup loc="post">+</ce:sup> effector cells with high anti-tumor activity.</ce:simple-para></ce:abstract-sec></ce:abstract></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Increased proliferation, lytic activity, and purity of human natural killer cells cocultured with mitogen-activated feeder cells</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Increased proliferation, lytic activity, and purity of human natural killer cells cocultured with mitogen-activated feeder cells</title></titleInfo><name type="personal"><namePart type="given">Hannah</namePart><namePart type="family">Rabinowich</namePart><affiliation>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><affiliation>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter</namePart><namePart type="family">Sedlmayr</namePart><affiliation>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><affiliation>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ronald B.</namePart><namePart type="family">Herberman</namePart><affiliation>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><affiliation>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><affiliation>Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Theresa L.</namePart><namePart type="family">Whiteside</namePart><affiliation>Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><affiliation>Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1991</dateIssued><copyrightDate encoding="w3cdtf">1991</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: The addition of mitogen-prestimulated periferal blood lymphocytes (PBL) or Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) cultures to enriched populations of natural killer (NK) cells obtained from PBL of normal donors in the presence of rIL-2 resulted in highly significant increases in proliferation, purity, and cytolytic activity of cultured NK cells. Two sources of enriched NK cell preparations were used: (i) Adherent-lymphokine activated killer (A-LAK) cells obtained by adherence to plastic during 24 hr activation with 103 Cetus U/ml rIL-2; and (ii) NK cells negatively selected from PBL by removal of high-affinity rosette-forming cells and CD3+ lymphocytes. Coculture of A-LAK cells for 14 days with autologous or allogeneic Con A-activated PBL (106 cells/ml) or selected EBV-transformed LCL (2 × 105 cells/ml) as feeder cells increased fold expansion by a mean ± SEM of 629 fold ± 275 (P < 0.019) and 267 fold ± 54 (P < 0.0001), respectively, compared to 55 ± 20 in A-LAK cultures without feeder cells. The addition of either activated PBL or EBV lines to A-LAK cultures also led to a significant increase in the percentage of NK cells (CD3−CD56+) (84 ± 2.4 and 84 ± 2.6%, respectively, P < 0.0001 for both), compared to 53 ± 7.2% in cultures without feeders. The presence of feeder cells in cultures of A-LAK cells also led to significantly higher anti-tumor cytolytic activity compared to control cultures, as measured against NK-sensitive (K562) and NK-resistant (Daudi) target cells. Mitogen-stimulated CD4+ PBL purified by positive selection on antibody-coated flasks were better feeders than CD8+ or unseparated PBL. In the presence of feeder cells, it was possible to generate up to 6 × 109 activated NK cells from 2 × 108 fresh PBL by Day 13 of culture. Enhanced NK cell proliferation in the presence of feeder cells was not attributable to a detectable soluble factor. The improved method for generating A-LAK or activated-NK cells should facilitate cellular adoptive immunotherapy by providing sufficient numbers of highly enriched CD3−CD56+ effector cells with high anti-tumor activity.</abstract><note>This research was supported in part by ACS Grant IM588A to T.L.W.</note><relatedItem type="host"><titleInfo><title>Cellular Immunology</title></titleInfo><titleInfo type="abbreviated"><title>YCIMM</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">199107</dateIssued></originInfo><identifier type="ISSN">0008-8749</identifier><identifier type="PII">S0008-8749(00)X0222-5</identifier><part><date>199107</date><detail type="volume"><number>135</number><caption>vol.</caption></detail><detail type="issue"><number>2</number><caption>no.</caption></detail><extent unit="issue-pages"><start>273</start><end>557</end></extent><extent unit="pages"><start>454</start><end>470</end></extent></part></relatedItem><identifier type="istex">717D4E17A0EA0E90EB8781587F92FBEC84499DCA</identifier><identifier type="ark">ark:/67375/6H6-35CGDHL7-5</identifier><identifier type="DOI">10.1016/0008-8749(91)90290-R</identifier><identifier type="PII">0008-8749(91)90290-R</identifier><identifier type="ArticleID">9190290R</identifier><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/717D4E17A0EA0E90EB8781587F92FBEC84499DCA/metadata/json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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