Monoclonal antibodies against ROR1 induce apoptosis of chronic lymphocytic leukemia (CLL) cells
ROR1 is a receptor tyrosine kinase (RTK) recently identified to be overexpressed at the gene and protein levels in chronic lymphocytic leukemia (CLL). Monoclonal antibodies (MAbs) against RTKs have been successfully applied for therapy of solid tumors. We generated five MAbs against the Ig ( n =1),...
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| Veröffentlicht in: | Leukemia 2012-06, Vol.26 (6), p.1348-1355 |
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| creator | Daneshmanesh, A H Hojjat-Farsangi, M Khan, A S Jeddi-Tehrani, M Akhondi, M M Bayat, A A Ghods, R Mahmoudi, A-R Hadavi, R Österborg, A Shokri, F Rabbani, H Mellstedt, H |
| description | ROR1 is a receptor tyrosine kinase (RTK) recently identified to be overexpressed at the gene and protein levels in chronic lymphocytic leukemia (CLL). Monoclonal antibodies (MAbs) against RTKs have been successfully applied for therapy of solid tumors. We generated five MAbs against the Ig (
n
=1), cysteine-rich (CRD) (
n
=2) and kringle (KNG) (
n
=2) domains, respectively, of the extracellular part of ROR1. All CLL patients (
n
=20) expressed ROR1 on the surface of the leukemic cells. A significantly higher frequency of ROR1 expression was found in patients with progressive versus non-progressive disease, and in those with unmutated versus mutated IgVH genes. All five MAbs alone induced apoptosis in the absence of complement or added effector cells (Annexin-V and MTT, as well as cleavage of poly-(ADP ribose)-polymerase, caspase-8 and caspase-9) of CLL cells but not of normal B cells. Most effective were MAbs against CRD and KNG, significantly superior to rituximab (
P |
| doi_str_mv | 10.1038/leu.2011.362 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_539296</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A293666925</galeid><sourcerecordid>A293666925</sourcerecordid><originalsourceid>FETCH-LOGICAL-c634t-efb6ec0af7c9b9abd817099234f5d415e0993febb2afd70ed433ca3651a7cdd53</originalsourceid><addsrcrecordid>eNqFkttv0zAUxiMEYt3gjWcUCTENiRTf4sSPU8VNKpo0wbPl2CetN9cOcSLU_x5H7dYODZAffPt95_j4fFn2CqM5RrT-4GCcE4TxnHLyJJthVvGiLEv8NJuhuq4KLgg7yU5jvEFouuTPsxNCSC0EFrNMfgs-aBe8crnyg22CsRBztVLWxyG_vrrGufVm1JCrLnRDiDbmoc31ug_e6txtN9066O0wrWG8hY1V-cViuXyXa3AuvsietcpFeLmfz7Ifnz5-X3wpllefvy4ul4XmlA0FtA0HjVRbadEI1ZgaV0gIQllbGoZLSBvaQtMQ1ZoKgWGUakV5iVWljSnpWVbs4sZf0I2N7Hq7Uf1WBmXl_ug2rUCWVBDBEy_-ynd9MAfRnRATVlWI0inXxU6bwJ8jxEFubJyqVR7CGCVGBNWMifTG_6NYIJHKYAl98wd6E8Y-9SVKwllZEcEE_ReVYtU8dR7xA7VSDqT1bRh6pafU8pIIynkyxVTH_BEqDZO6qIOH1qbzB4LzI8EalBvWMbhxsMHHh-D7Haj7EGMP7f3_YiQn18rkFTm5VibXJvz1vqix2YC5h-9smoC3e0BFrVzbK69tPHClqDlB7MgF6cqvoD_-nUcS_wbmygF0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1018655506</pqid></control><display><type>article</type><title>Monoclonal antibodies against ROR1 induce apoptosis of chronic lymphocytic leukemia (CLL) cells</title><source>MEDLINE</source><source>Nature</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Daneshmanesh, A H ; Hojjat-Farsangi, M ; Khan, A S ; Jeddi-Tehrani, M ; Akhondi, M M ; Bayat, A A ; Ghods, R ; Mahmoudi, A-R ; Hadavi, R ; Österborg, A ; Shokri, F ; Rabbani, H ; Mellstedt, H</creator><creatorcontrib>Daneshmanesh, A H ; Hojjat-Farsangi, M ; Khan, A S ; Jeddi-Tehrani, M ; Akhondi, M M ; Bayat, A A ; Ghods, R ; Mahmoudi, A-R ; Hadavi, R ; Österborg, A ; Shokri, F ; Rabbani, H ; Mellstedt, H</creatorcontrib><description>ROR1 is a receptor tyrosine kinase (RTK) recently identified to be overexpressed at the gene and protein levels in chronic lymphocytic leukemia (CLL). Monoclonal antibodies (MAbs) against RTKs have been successfully applied for therapy of solid tumors. We generated five MAbs against the Ig (
n
=1), cysteine-rich (CRD) (
n
=2) and kringle (KNG) (
n
=2) domains, respectively, of the extracellular part of ROR1. All CLL patients (
n
=20) expressed ROR1 on the surface of the leukemic cells. A significantly higher frequency of ROR1 expression was found in patients with progressive versus non-progressive disease, and in those with unmutated versus mutated IgVH genes. All five MAbs alone induced apoptosis in the absence of complement or added effector cells (Annexin-V and MTT, as well as cleavage of poly-(ADP ribose)-polymerase, caspase-8 and caspase-9) of CLL cells but not of normal B cells. Most effective were MAbs against CRD and KNG, significantly superior to rituximab (
P
<0.005). Cross-linking of anti-ROR1 MAbs using the F(ab′)
2
fragments of anti-Fc antibodies significantly augmented apoptosis. Two of the MAbs induced complement-dependent cytotoxicity (CDC) similar to that of rituximab and one anti-ROR1 MAb (KNG) (IgG1) showed killing activity by antibody-dependent cellular cytotoxicity. The identified ROR1 epitopes may provide a basis for generating human ROR1 MAbs for therapy.</description><identifier>ISSN: 0887-6924</identifier><identifier>ISSN: 1476-5551</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2011.362</identifier><identifier>PMID: 22289919</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1059/2325 ; 631/80/82/23 ; 692/699/67/1990/283/1895 ; Animals ; Antibodies, Monoclonal - pharmacology ; Antibody Formation ; Antibody-Dependent Cell Cytotoxicity ; Apoptosis ; Apoptosis - immunology ; Biological and medical sciences ; Cancer Research ; Care and treatment ; Caspase-8 ; Caspase-9 ; Chronic lymphocytic leukemia ; Critical Care Medicine ; Crosslinking ; Cytotoxicity ; Effector cells ; Epitopes ; Genetic aspects ; Health care ; Hematologic and hematopoietic diseases ; Hematology ; Humans ; Immunization ; Immunoglobulin G ; Immunoglobulins ; Immunotherapy ; Intensive ; Internal Medicine ; Kinases ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell - immunology ; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell - pathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lymphatic leukemia ; Lymphocytes B ; Medical prognosis ; Medical sciences ; Medicin och hälsovetenskap ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred BALB C ; Monoclonal antibodies ; Oncology ; original-article ; Peptide Fragments - immunology ; Peptides ; Physiological aspects ; Protein-tyrosine kinase receptors ; Proteins ; Receptor Tyrosine Kinase-like Orphan Receptors - immunology ; Receptor Tyrosine Kinase-like Orphan Receptors - metabolism ; Ribose ; Rituximab ; Solid tumors ; Toxicity ; Tumor Cells, Cultured ; Tumors ; Tyrosine</subject><ispartof>Leukemia, 2012-06, Vol.26 (6), p.1348-1355</ispartof><rights>Macmillan Publishers Limited 2012</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2012 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2012</rights><rights>Macmillan Publishers Limited 2012.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c634t-efb6ec0af7c9b9abd817099234f5d415e0993febb2afd70ed433ca3651a7cdd53</citedby><cites>FETCH-LOGICAL-c634t-efb6ec0af7c9b9abd817099234f5d415e0993febb2afd70ed433ca3651a7cdd53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25986204$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22289919$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:124770335$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Daneshmanesh, A H</creatorcontrib><creatorcontrib>Hojjat-Farsangi, M</creatorcontrib><creatorcontrib>Khan, A S</creatorcontrib><creatorcontrib>Jeddi-Tehrani, M</creatorcontrib><creatorcontrib>Akhondi, M M</creatorcontrib><creatorcontrib>Bayat, A A</creatorcontrib><creatorcontrib>Ghods, R</creatorcontrib><creatorcontrib>Mahmoudi, A-R</creatorcontrib><creatorcontrib>Hadavi, R</creatorcontrib><creatorcontrib>Österborg, A</creatorcontrib><creatorcontrib>Shokri, F</creatorcontrib><creatorcontrib>Rabbani, H</creatorcontrib><creatorcontrib>Mellstedt, H</creatorcontrib><title>Monoclonal antibodies against ROR1 induce apoptosis of chronic lymphocytic leukemia (CLL) cells</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>ROR1 is a receptor tyrosine kinase (RTK) recently identified to be overexpressed at the gene and protein levels in chronic lymphocytic leukemia (CLL). Monoclonal antibodies (MAbs) against RTKs have been successfully applied for therapy of solid tumors. We generated five MAbs against the Ig (
n
=1), cysteine-rich (CRD) (
n
=2) and kringle (KNG) (
n
=2) domains, respectively, of the extracellular part of ROR1. All CLL patients (
n
=20) expressed ROR1 on the surface of the leukemic cells. A significantly higher frequency of ROR1 expression was found in patients with progressive versus non-progressive disease, and in those with unmutated versus mutated IgVH genes. All five MAbs alone induced apoptosis in the absence of complement or added effector cells (Annexin-V and MTT, as well as cleavage of poly-(ADP ribose)-polymerase, caspase-8 and caspase-9) of CLL cells but not of normal B cells. Most effective were MAbs against CRD and KNG, significantly superior to rituximab (
P
<0.005). Cross-linking of anti-ROR1 MAbs using the F(ab′)
2
fragments of anti-Fc antibodies significantly augmented apoptosis. Two of the MAbs induced complement-dependent cytotoxicity (CDC) similar to that of rituximab and one anti-ROR1 MAb (KNG) (IgG1) showed killing activity by antibody-dependent cellular cytotoxicity. The identified ROR1 epitopes may provide a basis for generating human ROR1 MAbs for therapy.</description><subject>631/67/1059/2325</subject><subject>631/80/82/23</subject><subject>692/699/67/1990/283/1895</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibody Formation</subject><subject>Antibody-Dependent Cell Cytotoxicity</subject><subject>Apoptosis</subject><subject>Apoptosis - immunology</subject><subject>Biological and medical sciences</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>Caspase-8</subject><subject>Caspase-9</subject><subject>Chronic lymphocytic leukemia</subject><subject>Critical Care Medicine</subject><subject>Crosslinking</subject><subject>Cytotoxicity</subject><subject>Effector cells</subject><subject>Epitopes</subject><subject>Genetic aspects</subject><subject>Health care</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulins</subject><subject>Immunotherapy</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - immunology</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - metabolism</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - pathology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Lymphatic leukemia</subject><subject>Lymphocytes B</subject><subject>Medical prognosis</subject><subject>Medical sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Monoclonal antibodies</subject><subject>Oncology</subject><subject>original-article</subject><subject>Peptide Fragments - immunology</subject><subject>Peptides</subject><subject>Physiological aspects</subject><subject>Protein-tyrosine kinase receptors</subject><subject>Proteins</subject><subject>Receptor Tyrosine Kinase-like Orphan Receptors - immunology</subject><subject>Receptor Tyrosine Kinase-like Orphan Receptors - metabolism</subject><subject>Ribose</subject><subject>Rituximab</subject><subject>Solid tumors</subject><subject>Toxicity</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>Tyrosine</subject><issn>0887-6924</issn><issn>1476-5551</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkttv0zAUxiMEYt3gjWcUCTENiRTf4sSPU8VNKpo0wbPl2CetN9cOcSLU_x5H7dYODZAffPt95_j4fFn2CqM5RrT-4GCcE4TxnHLyJJthVvGiLEv8NJuhuq4KLgg7yU5jvEFouuTPsxNCSC0EFrNMfgs-aBe8crnyg22CsRBztVLWxyG_vrrGufVm1JCrLnRDiDbmoc31ug_e6txtN9066O0wrWG8hY1V-cViuXyXa3AuvsietcpFeLmfz7Ifnz5-X3wpllefvy4ul4XmlA0FtA0HjVRbadEI1ZgaV0gIQllbGoZLSBvaQtMQ1ZoKgWGUakV5iVWljSnpWVbs4sZf0I2N7Hq7Uf1WBmXl_ug2rUCWVBDBEy_-ynd9MAfRnRATVlWI0inXxU6bwJ8jxEFubJyqVR7CGCVGBNWMifTG_6NYIJHKYAl98wd6E8Y-9SVKwllZEcEE_ReVYtU8dR7xA7VSDqT1bRh6pafU8pIIynkyxVTH_BEqDZO6qIOH1qbzB4LzI8EalBvWMbhxsMHHh-D7Haj7EGMP7f3_YiQn18rkFTm5VibXJvz1vqix2YC5h-9smoC3e0BFrVzbK69tPHClqDlB7MgF6cqvoD_-nUcS_wbmygF0</recordid><startdate>20120601</startdate><enddate>20120601</enddate><creator>Daneshmanesh, A H</creator><creator>Hojjat-Farsangi, M</creator><creator>Khan, A S</creator><creator>Jeddi-Tehrani, M</creator><creator>Akhondi, M M</creator><creator>Bayat, A A</creator><creator>Ghods, R</creator><creator>Mahmoudi, A-R</creator><creator>Hadavi, R</creator><creator>Österborg, A</creator><creator>Shokri, F</creator><creator>Rabbani, H</creator><creator>Mellstedt, H</creator><general>Nature Publishing Group UK</general><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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20120601</creationdate><title>Monoclonal antibodies against ROR1 induce apoptosis of chronic lymphocytic leukemia (CLL) cells</title><author>Daneshmanesh, A H ; Hojjat-Farsangi, M ; Khan, A S ; Jeddi-Tehrani, M ; Akhondi, M M ; Bayat, A A ; Ghods, R ; Mahmoudi, A-R ; Hadavi, R ; Österborg, A ; Shokri, F ; Rabbani, H ; Mellstedt, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c634t-efb6ec0af7c9b9abd817099234f5d415e0993febb2afd70ed433ca3651a7cdd53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>631/67/1059/2325</topic><topic>631/80/82/23</topic><topic>692/699/67/1990/283/1895</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antibody Formation</topic><topic>Antibody-Dependent Cell Cytotoxicity</topic><topic>Apoptosis</topic><topic>Apoptosis - immunology</topic><topic>Biological and medical sciences</topic><topic>Cancer Research</topic><topic>Care and treatment</topic><topic>Caspase-8</topic><topic>Caspase-9</topic><topic>Chronic lymphocytic leukemia</topic><topic>Critical Care Medicine</topic><topic>Crosslinking</topic><topic>Cytotoxicity</topic><topic>Effector cells</topic><topic>Epitopes</topic><topic>Genetic aspects</topic><topic>Health care</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunization</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulins</topic><topic>Immunotherapy</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Kinases</topic><topic>Leukemia</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - immunology</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - metabolism</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - pathology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Lymphatic leukemia</topic><topic>Lymphocytes B</topic><topic>Medical prognosis</topic><topic>Medical sciences</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Monoclonal antibodies</topic><topic>Oncology</topic><topic>original-article</topic><topic>Peptide Fragments - immunology</topic><topic>Peptides</topic><topic>Physiological aspects</topic><topic>Protein-tyrosine kinase receptors</topic><topic>Proteins</topic><topic>Receptor Tyrosine Kinase-like Orphan Receptors - immunology</topic><topic>Receptor Tyrosine Kinase-like Orphan Receptors - metabolism</topic><topic>Ribose</topic><topic>Rituximab</topic><topic>Solid tumors</topic><topic>Toxicity</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><topic>Tyrosine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Daneshmanesh, A H</creatorcontrib><creatorcontrib>Hojjat-Farsangi, M</creatorcontrib><creatorcontrib>Khan, A S</creatorcontrib><creatorcontrib>Jeddi-Tehrani, M</creatorcontrib><creatorcontrib>Akhondi, M M</creatorcontrib><creatorcontrib>Bayat, A A</creatorcontrib><creatorcontrib>Ghods, R</creatorcontrib><creatorcontrib>Mahmoudi, A-R</creatorcontrib><creatorcontrib>Hadavi, R</creatorcontrib><creatorcontrib>Österborg, A</creatorcontrib><creatorcontrib>Shokri, F</creatorcontrib><creatorcontrib>Rabbani, H</creatorcontrib><creatorcontrib>Mellstedt, H</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>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Daneshmanesh, A H</au><au>Hojjat-Farsangi, M</au><au>Khan, A S</au><au>Jeddi-Tehrani, M</au><au>Akhondi, M M</au><au>Bayat, A A</au><au>Ghods, R</au><au>Mahmoudi, A-R</au><au>Hadavi, R</au><au>Österborg, A</au><au>Shokri, F</au><au>Rabbani, H</au><au>Mellstedt, H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Monoclonal antibodies against ROR1 induce apoptosis of chronic lymphocytic leukemia (CLL) cells</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2012-06-01</date><risdate>2012</risdate><volume>26</volume><issue>6</issue><spage>1348</spage><epage>1355</epage><pages>1348-1355</pages><issn>0887-6924</issn><issn>1476-5551</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>ROR1 is a receptor tyrosine kinase (RTK) recently identified to be overexpressed at the gene and protein levels in chronic lymphocytic leukemia (CLL). Monoclonal antibodies (MAbs) against RTKs have been successfully applied for therapy of solid tumors. We generated five MAbs against the Ig (
n
=1), cysteine-rich (CRD) (
n
=2) and kringle (KNG) (
n
=2) domains, respectively, of the extracellular part of ROR1. All CLL patients (
n
=20) expressed ROR1 on the surface of the leukemic cells. A significantly higher frequency of ROR1 expression was found in patients with progressive versus non-progressive disease, and in those with unmutated versus mutated IgVH genes. All five MAbs alone induced apoptosis in the absence of complement or added effector cells (Annexin-V and MTT, as well as cleavage of poly-(ADP ribose)-polymerase, caspase-8 and caspase-9) of CLL cells but not of normal B cells. Most effective were MAbs against CRD and KNG, significantly superior to rituximab (
P
<0.005). Cross-linking of anti-ROR1 MAbs using the F(ab′)
2
fragments of anti-Fc antibodies significantly augmented apoptosis. Two of the MAbs induced complement-dependent cytotoxicity (CDC) similar to that of rituximab and one anti-ROR1 MAb (KNG) (IgG1) showed killing activity by antibody-dependent cellular cytotoxicity. The identified ROR1 epitopes may provide a basis for generating human ROR1 MAbs for therapy.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22289919</pmid><doi>10.1038/leu.2011.362</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2012-06, Vol.26 (6), p.1348-1355 |
| issn | 0887-6924 1476-5551 1476-5551 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_539296 |
| source | MEDLINE; Nature; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | 631/67/1059/2325 631/80/82/23 692/699/67/1990/283/1895 Animals Antibodies, Monoclonal - pharmacology Antibody Formation Antibody-Dependent Cell Cytotoxicity Apoptosis Apoptosis - immunology Biological and medical sciences Cancer Research Care and treatment Caspase-8 Caspase-9 Chronic lymphocytic leukemia Critical Care Medicine Crosslinking Cytotoxicity Effector cells Epitopes Genetic aspects Health care Hematologic and hematopoietic diseases Hematology Humans Immunization Immunoglobulin G Immunoglobulins Immunotherapy Intensive Internal Medicine Kinases Leukemia Leukemia, Lymphocytic, Chronic, B-Cell - immunology Leukemia, Lymphocytic, Chronic, B-Cell - metabolism Leukemia, Lymphocytic, Chronic, B-Cell - pathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymphatic leukemia Lymphocytes B Medical prognosis Medical sciences Medicin och hälsovetenskap Medicine Medicine & Public Health Mice Mice, Inbred BALB C Monoclonal antibodies Oncology original-article Peptide Fragments - immunology Peptides Physiological aspects Protein-tyrosine kinase receptors Proteins Receptor Tyrosine Kinase-like Orphan Receptors - immunology Receptor Tyrosine Kinase-like Orphan Receptors - metabolism Ribose Rituximab Solid tumors Toxicity Tumor Cells, Cultured Tumors Tyrosine |
| title | Monoclonal antibodies against ROR1 induce apoptosis of chronic lymphocytic leukemia (CLL) cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T10%3A06%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Monoclonal%20antibodies%20against%20ROR1%20induce%20apoptosis%20of%20chronic%20lymphocytic%20leukemia%20(CLL)%20cells&rft.jtitle=Leukemia&rft.au=Daneshmanesh,%20A%20H&rft.date=2012-06-01&rft.volume=26&rft.issue=6&rft.spage=1348&rft.epage=1355&rft.pages=1348-1355&rft.issn=0887-6924&rft.eissn=1476-5551&rft.coden=LEUKED&rft_id=info:doi/10.1038/leu.2011.362&rft_dat=%3Cgale_swepu%3EA293666925%3C/gale_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1018655506&rft_id=info:pmid/22289919&rft_galeid=A293666925&rfr_iscdi=true |