Variable Contribution of Monoclonal Antibodies to ADCC in patients with chronic lymphocytic leukemia
Monoclonal antibodies (mAbs) are increasingly used in treatment protocols for chronic lymphocytic leukemia (CLL). Here we determined (i) the extent of antibody-dependent cellular cytotoxicity (ADCC) of four different mAbs against primary CLL cells, (ii) whether ADCC correlates with antigen density o...
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Veröffentlicht in: | Leukemia & lymphoma 2009-01, Vol.50 (8), p.1361-1368 |
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description | Monoclonal antibodies (mAbs) are increasingly used in treatment protocols for chronic lymphocytic leukemia (CLL). Here we determined (i) the extent of antibody-dependent cellular cytotoxicity (ADCC) of four different mAbs against primary CLL cells, (ii) whether ADCC correlates with antigen density on CLL cells, and (iii) whether allogeneic natural killer (NK) cells display superior ADCC than autologous. Effector cells for ADCC were (i) NK-92 cells not expressing FcR, (ii) NK-92 cells transfected with a high-affinity Fc receptor, (iii) autologous NK cells from patients with CLL, (iv) allogeneic NK cells. Results suggest that ADCC contributes to killing of CLL cells by anti-CD20 antibodies (rituximab and veltuzumab), whereas mAbs against CD22 (epratuzumab) and CD23 (lumiliximab) showed minimal ADCC. The magnitude of anti-CD20 mediated ADCC did not correlate with antigen density of CD20. ADCC was not influenced by the FcR genotype expressed by autologous NK cells. Allogeneic NK cells were superior to autologous NK cells in killing primary CLL cells. |
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Here we determined (i) the extent of antibody-dependent cellular cytotoxicity (ADCC) of four different mAbs against primary CLL cells, (ii) whether ADCC correlates with antigen density on CLL cells, and (iii) whether allogeneic natural killer (NK) cells display superior ADCC than autologous. Effector cells for ADCC were (i) NK-92 cells not expressing FcR, (ii) NK-92 cells transfected with a high-affinity Fc receptor, (iii) autologous NK cells from patients with CLL, (iv) allogeneic NK cells. Results suggest that ADCC contributes to killing of CLL cells by anti-CD20 antibodies (rituximab and veltuzumab), whereas mAbs against CD22 (epratuzumab) and CD23 (lumiliximab) showed minimal ADCC. The magnitude of anti-CD20 mediated ADCC did not correlate with antigen density of CD20. ADCC was not influenced by the FcR genotype expressed by autologous NK cells. Allogeneic NK cells were superior to autologous NK cells in killing primary CLL cells.</description><identifier>ISSN: 1042-8194</identifier><identifier>EISSN: 1029-2403</identifier><identifier>DOI: 10.1080/10428190903026500</identifier><identifier>PMID: 19562616</identifier><language>eng</language><publisher>United States: Informa UK Ltd</publisher><subject>ADCC ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal, Humanized ; Antibodies, Monoclonal, Murine-Derived ; Antibody-Dependent Cell Cytotoxicity ; Antigens, CD - immunology ; Antigens, CD20 - immunology ; Antigens, Neoplasm - immunology ; Antineoplastic Agents - immunology ; CD52 Antigen ; Cell Line, Tumor - immunology ; CLL ; Genotype ; Glycoproteins - immunology ; Humans ; In Vitro Techniques ; Killer Cells, Natural - immunology ; Leukemia, Lymphocytic, Chronic, B-Cell - immunology ; Leukemia, Lymphocytic, Chronic, B-Cell - pathology ; Middle Aged ; monoclonal antibodies ; natural killer cells ; Receptors, IgG - genetics ; Receptors, IgG - immunology ; Recombinant Fusion Proteins - immunology ; Rituximab ; Sialic Acid Binding Ig-like Lectin 2 - immunology ; Transfection</subject><ispartof>Leukemia & lymphoma, 2009-01, Vol.50 (8), p.1361-1368</ispartof><rights>2009 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-3c065fdb1ec54bfcee74f858bf5441da81301017dbb065206d6cac51c0ee817e3</citedby><cites>FETCH-LOGICAL-c405t-3c065fdb1ec54bfcee74f858bf5441da81301017dbb065206d6cac51c0ee817e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.1080/10428190903026500$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1080/10428190903026500$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,59647,59753,60436,60542,61221,61256,61402,61437</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19562616$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Weitzman, James</creatorcontrib><creatorcontrib>Betancur, Monica</creatorcontrib><creatorcontrib>Boissel, Laurent</creatorcontrib><creatorcontrib>Rabinowitz, Arthur P.</creatorcontrib><creatorcontrib>Klein, Andreas</creatorcontrib><creatorcontrib>Klingemann, Hans</creatorcontrib><title>Variable Contribution of Monoclonal Antibodies to ADCC in patients with chronic lymphocytic leukemia</title><title>Leukemia & lymphoma</title><addtitle>Leuk Lymphoma</addtitle><description>Monoclonal antibodies (mAbs) are increasingly used in treatment protocols for chronic lymphocytic leukemia (CLL). Here we determined (i) the extent of antibody-dependent cellular cytotoxicity (ADCC) of four different mAbs against primary CLL cells, (ii) whether ADCC correlates with antigen density on CLL cells, and (iii) whether allogeneic natural killer (NK) cells display superior ADCC than autologous. Effector cells for ADCC were (i) NK-92 cells not expressing FcR, (ii) NK-92 cells transfected with a high-affinity Fc receptor, (iii) autologous NK cells from patients with CLL, (iv) allogeneic NK cells. Results suggest that ADCC contributes to killing of CLL cells by anti-CD20 antibodies (rituximab and veltuzumab), whereas mAbs against CD22 (epratuzumab) and CD23 (lumiliximab) showed minimal ADCC. The magnitude of anti-CD20 mediated ADCC did not correlate with antigen density of CD20. ADCC was not influenced by the FcR genotype expressed by autologous NK cells. Allogeneic NK cells were superior to autologous NK cells in killing primary CLL cells.</description><subject>ADCC</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Antibodies, Monoclonal, Murine-Derived</subject><subject>Antibody-Dependent Cell Cytotoxicity</subject><subject>Antigens, CD - immunology</subject><subject>Antigens, CD20 - immunology</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Antineoplastic Agents - immunology</subject><subject>CD52 Antigen</subject><subject>Cell Line, Tumor - immunology</subject><subject>CLL</subject><subject>Genotype</subject><subject>Glycoproteins - immunology</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Killer Cells, Natural - immunology</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - immunology</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - pathology</subject><subject>Middle Aged</subject><subject>monoclonal antibodies</subject><subject>natural killer cells</subject><subject>Receptors, IgG - genetics</subject><subject>Receptors, IgG - immunology</subject><subject>Recombinant Fusion Proteins - immunology</subject><subject>Rituximab</subject><subject>Sialic Acid Binding Ig-like Lectin 2 - immunology</subject><subject>Transfection</subject><issn>1042-8194</issn><issn>1029-2403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9v1DAUxC0Eov_4AFyQb5xSnh0nmwguq7QFpCIu0KtlO8-Ki2MvtqNqvz1Z7UoIIfX05vCb0dMMIW8ZXDPo4AMDwTvWQw818LYBeEHOGfC-4gLqlwcteLUC4oxc5PwIAE3f8tfkjPVNy1vWnpPxQSWntEc6xFCS00txMdBo6bcYovExKE-3oTgdR4eZlki3N8NAXaA7VRyGkumTKxM1U4rBGer3826KZl8OGpdfODt1RV5Z5TO-Od1L8vPu9sfwpbr__vnrsL2vjICmVLWBtrGjZmgaoa1B3AjbNZ22jRBsVB2rgQHbjFqvIId2bI0yDTOA2LEN1pfk_TF3l-LvBXORs8sGvVcB45Llpq7bjteiW0l2JE2KOSe0cpfcrNJeMpCHbuV_3a6ed6f0Rc84_nWcylyBT0fABRvTrJ5i8qMsau9jskkF47Ksn8v_-I99QuXLZFRC-RiXtA6Rn_nuD8UsmlU</recordid><startdate>20090101</startdate><enddate>20090101</enddate><creator>Weitzman, James</creator><creator>Betancur, Monica</creator><creator>Boissel, Laurent</creator><creator>Rabinowitz, Arthur P.</creator><creator>Klein, Andreas</creator><creator>Klingemann, Hans</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><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>20090101</creationdate><title>Variable Contribution of Monoclonal Antibodies to ADCC in patients with chronic lymphocytic leukemia</title><author>Weitzman, James ; Betancur, Monica ; Boissel, Laurent ; Rabinowitz, Arthur P. ; Klein, Andreas ; Klingemann, Hans</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-3c065fdb1ec54bfcee74f858bf5441da81301017dbb065206d6cac51c0ee817e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>ADCC</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Antibodies, Monoclonal, Murine-Derived</topic><topic>Antibody-Dependent Cell Cytotoxicity</topic><topic>Antigens, CD - immunology</topic><topic>Antigens, CD20 - immunology</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Antineoplastic Agents - immunology</topic><topic>CD52 Antigen</topic><topic>Cell Line, Tumor - immunology</topic><topic>CLL</topic><topic>Genotype</topic><topic>Glycoproteins - immunology</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Killer Cells, Natural - immunology</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - immunology</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - pathology</topic><topic>Middle Aged</topic><topic>monoclonal antibodies</topic><topic>natural killer cells</topic><topic>Receptors, IgG - genetics</topic><topic>Receptors, IgG - immunology</topic><topic>Recombinant Fusion Proteins - immunology</topic><topic>Rituximab</topic><topic>Sialic Acid Binding Ig-like Lectin 2 - immunology</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Weitzman, James</creatorcontrib><creatorcontrib>Betancur, Monica</creatorcontrib><creatorcontrib>Boissel, Laurent</creatorcontrib><creatorcontrib>Rabinowitz, Arthur P.</creatorcontrib><creatorcontrib>Klein, Andreas</creatorcontrib><creatorcontrib>Klingemann, Hans</creatorcontrib><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>Leukemia & lymphoma</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Weitzman, James</au><au>Betancur, Monica</au><au>Boissel, Laurent</au><au>Rabinowitz, Arthur P.</au><au>Klein, Andreas</au><au>Klingemann, Hans</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Variable Contribution of Monoclonal Antibodies to ADCC in patients with chronic lymphocytic leukemia</atitle><jtitle>Leukemia & lymphoma</jtitle><addtitle>Leuk Lymphoma</addtitle><date>2009-01-01</date><risdate>2009</risdate><volume>50</volume><issue>8</issue><spage>1361</spage><epage>1368</epage><pages>1361-1368</pages><issn>1042-8194</issn><eissn>1029-2403</eissn><abstract>Monoclonal antibodies (mAbs) are increasingly used in treatment protocols for chronic lymphocytic leukemia (CLL). Here we determined (i) the extent of antibody-dependent cellular cytotoxicity (ADCC) of four different mAbs against primary CLL cells, (ii) whether ADCC correlates with antigen density on CLL cells, and (iii) whether allogeneic natural killer (NK) cells display superior ADCC than autologous. Effector cells for ADCC were (i) NK-92 cells not expressing FcR, (ii) NK-92 cells transfected with a high-affinity Fc receptor, (iii) autologous NK cells from patients with CLL, (iv) allogeneic NK cells. Results suggest that ADCC contributes to killing of CLL cells by anti-CD20 antibodies (rituximab and veltuzumab), whereas mAbs against CD22 (epratuzumab) and CD23 (lumiliximab) showed minimal ADCC. The magnitude of anti-CD20 mediated ADCC did not correlate with antigen density of CD20. ADCC was not influenced by the FcR genotype expressed by autologous NK cells. Allogeneic NK cells were superior to autologous NK cells in killing primary CLL cells.</abstract><cop>United States</cop><pub>Informa UK Ltd</pub><pmid>19562616</pmid><doi>10.1080/10428190903026500</doi><tpages>8</tpages></addata></record> |
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subjects | ADCC Antibodies, Monoclonal - immunology Antibodies, Monoclonal, Humanized Antibodies, Monoclonal, Murine-Derived Antibody-Dependent Cell Cytotoxicity Antigens, CD - immunology Antigens, CD20 - immunology Antigens, Neoplasm - immunology Antineoplastic Agents - immunology CD52 Antigen Cell Line, Tumor - immunology CLL Genotype Glycoproteins - immunology Humans In Vitro Techniques Killer Cells, Natural - immunology Leukemia, Lymphocytic, Chronic, B-Cell - immunology Leukemia, Lymphocytic, Chronic, B-Cell - pathology Middle Aged monoclonal antibodies natural killer cells Receptors, IgG - genetics Receptors, IgG - immunology Recombinant Fusion Proteins - immunology Rituximab Sialic Acid Binding Ig-like Lectin 2 - immunology Transfection |
title | Variable Contribution of Monoclonal Antibodies to ADCC in patients with chronic lymphocytic leukemia |
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