Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells
Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) affects hematopoietic development and therefore is associated with immune deficiencies that can be further exacerbated by chemotherapy. It is unclear if and when monoclonal antibodies (mAbs) that stimulate antibody-mediated cellular cytoto...
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description | Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) affects hematopoietic development and therefore is associated with immune deficiencies that can be further exacerbated by chemotherapy. It is unclear if and when monoclonal antibodies (mAbs) that stimulate antibody-mediated cellular cytotoxicity (ADCC) can be used for treatment because this depends on the presence of functional effector cells. Here, we used flow cytometry to determine that patient samples at diagnosis, post-induction and relapse contain detectable numbers of CD56+ cells. We were able to selectively expand CD56+ immune effector cells from bone marrow and peripheral blood samples at diagnosis and at various stages of treatment by co-culture with artificial antigen-presenting K562 clone 9.mbIL-21 cells. Amplified CD56+CD3− cells had spontaneous and anti-B cell-activating factor receptor mAb-stimulated ADCC activity against allogeneic ALL cells, which could be further enhanced by IL-15. Importantly, matched CD56+ effector cells also killed autologous ALL cells grown out from leukemia samples of the same patient, through both spontaneous as well as antibody-dependent cellular cytotoxicity. Since autologous cell therapy will not be complicated by graft-versus-host disease, our results show that expanded CD56+ cells could be applied for treatment of pre-B ALL without transplantation, or for purging of bone marrow in the setting of autologous bone marrow transplants. |
doi_str_mv | 10.1038/leu.2014.246 |
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It is unclear if and when monoclonal antibodies (mAbs) that stimulate antibody-mediated cellular cytotoxicity (ADCC) can be used for treatment because this depends on the presence of functional effector cells. Here, we used flow cytometry to determine that patient samples at diagnosis, post-induction and relapse contain detectable numbers of CD56+ cells. We were able to selectively expand CD56+ immune effector cells from bone marrow and peripheral blood samples at diagnosis and at various stages of treatment by co-culture with artificial antigen-presenting K562 clone 9.mbIL-21 cells. Amplified CD56+CD3− cells had spontaneous and anti-B cell-activating factor receptor mAb-stimulated ADCC activity against allogeneic ALL cells, which could be further enhanced by IL-15. Importantly, matched CD56+ effector cells also killed autologous ALL cells grown out from leukemia samples of the same patient, through both spontaneous as well as antibody-dependent cellular cytotoxicity. Since autologous cell therapy will not be complicated by graft-versus-host disease, our results show that expanded CD56+ cells could be applied for treatment of pre-B ALL without transplantation, or for purging of bone marrow in the setting of autologous bone marrow transplants.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2014.246</identifier><identifier>PMID: 25134458</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/1 ; 13/106 ; 13/31 ; 631/154/51/1844 ; 631/67/1990/283 ; 631/67/580 ; 692/699/67/1990/283/2125 ; Acute lymphoblastic leukemia ; Acute lymphocytic leukemia ; Antibodies, Monoclonal - biosynthesis ; Antigens ; Antineoplastic Agents - therapeutic use ; Autografts ; B-Lymphocytes - drug effects ; B-Lymphocytes - immunology ; B-Lymphocytes - pathology ; Bone marrow ; Bone Marrow Cells - drug effects ; Bone Marrow Cells - immunology ; Bone Marrow Cells - pathology ; Bone marrow transplantation ; Cancer Research ; Care and treatment ; CD3 antigen ; CD3 Complex - genetics ; CD3 Complex - metabolism ; CD56 antigen ; CD56 Antigen - genetics ; CD56 Antigen - metabolism ; Cell culture ; Cell mediated cytotoxicity ; Cell Proliferation - drug effects ; Cell therapy ; Cellular proteins ; Chemotherapy ; Child ; Coculture Techniques ; Critical Care Medicine ; Cytotoxicity ; Cytotoxicity, Immunologic ; Development and progression ; Diagnosis ; Drug therapy ; Effector cells ; Flow cytometry ; Gene Expression ; Genetic aspects ; Graft-versus-host reaction ; Health aspects ; Hematology ; Hemopoiesis ; Humans ; Intensive ; Interleukin 15 ; Interleukin-15 - pharmacology ; Internal Medicine ; K562 Cells ; Killer Cells, Natural - drug effects ; Killer Cells, Natural - immunology ; Killer Cells, Natural - pathology ; Leukemia ; Lymphatic leukemia ; Lymphocytes ; Lymphocytes B ; Medicine ; Medicine & Public Health ; Monoclonal antibodies ; Oncology ; original-article ; Peripheral blood ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Precursors ; Purging ; Remission Induction ; Toxicity ; Transplantation ; Transplants ; Transplants & implants</subject><ispartof>Leukemia, 2015-04, Vol.29 (4), p.788-797</ispartof><rights>Macmillan Publishers Limited 2015</rights><rights>COPYRIGHT 2015 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 2015</rights><rights>Macmillan Publishers Limited 2015.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c710t-d98349673399d5d6fa9f813a72f17c6b7830cabd030e8f88055611a19630f92c3</citedby><cites>FETCH-LOGICAL-c710t-d98349673399d5d6fa9f813a72f17c6b7830cabd030e8f88055611a19630f92c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/leu.2014.246$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2014.246$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25134458$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fei, F</creatorcontrib><creatorcontrib>Lim, M</creatorcontrib><creatorcontrib>George, A A</creatorcontrib><creatorcontrib>Kirzner, J</creatorcontrib><creatorcontrib>Lee, D</creatorcontrib><creatorcontrib>Seeger, R</creatorcontrib><creatorcontrib>Groffen, J</creatorcontrib><creatorcontrib>Abdel-Azim, H</creatorcontrib><creatorcontrib>Heisterkamp, N</creatorcontrib><title>Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) affects hematopoietic development and therefore is associated with immune deficiencies that can be further exacerbated by chemotherapy. It is unclear if and when monoclonal antibodies (mAbs) that stimulate antibody-mediated cellular cytotoxicity (ADCC) can be used for treatment because this depends on the presence of functional effector cells. Here, we used flow cytometry to determine that patient samples at diagnosis, post-induction and relapse contain detectable numbers of CD56+ cells. We were able to selectively expand CD56+ immune effector cells from bone marrow and peripheral blood samples at diagnosis and at various stages of treatment by co-culture with artificial antigen-presenting K562 clone 9.mbIL-21 cells. Amplified CD56+CD3− cells had spontaneous and anti-B cell-activating factor receptor mAb-stimulated ADCC activity against allogeneic ALL cells, which could be further enhanced by IL-15. Importantly, matched CD56+ effector cells also killed autologous ALL cells grown out from leukemia samples of the same patient, through both spontaneous as well as antibody-dependent cellular cytotoxicity. Since autologous cell therapy will not be complicated by graft-versus-host disease, our results show that expanded CD56+ cells could be applied for treatment of pre-B ALL without transplantation, or for purging of bone marrow in the setting of autologous bone marrow transplants.</description><subject>13</subject><subject>13/1</subject><subject>13/106</subject><subject>13/31</subject><subject>631/154/51/1844</subject><subject>631/67/1990/283</subject><subject>631/67/580</subject><subject>692/699/67/1990/283/2125</subject><subject>Acute lymphoblastic leukemia</subject><subject>Acute lymphocytic leukemia</subject><subject>Antibodies, Monoclonal - biosynthesis</subject><subject>Antigens</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Autografts</subject><subject>B-Lymphocytes - drug effects</subject><subject>B-Lymphocytes - immunology</subject><subject>B-Lymphocytes - pathology</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - drug effects</subject><subject>Bone Marrow Cells - immunology</subject><subject>Bone Marrow Cells - pathology</subject><subject>Bone marrow transplantation</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>CD3 antigen</subject><subject>CD3 Complex - genetics</subject><subject>CD3 Complex - metabolism</subject><subject>CD56 antigen</subject><subject>CD56 Antigen - genetics</subject><subject>CD56 Antigen - metabolism</subject><subject>Cell culture</subject><subject>Cell mediated cytotoxicity</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell therapy</subject><subject>Cellular proteins</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Coculture Techniques</subject><subject>Critical Care Medicine</subject><subject>Cytotoxicity</subject><subject>Cytotoxicity, Immunologic</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Drug therapy</subject><subject>Effector cells</subject><subject>Flow cytometry</subject><subject>Gene Expression</subject><subject>Genetic aspects</subject><subject>Graft-versus-host reaction</subject><subject>Health aspects</subject><subject>Hematology</subject><subject>Hemopoiesis</subject><subject>Humans</subject><subject>Intensive</subject><subject>Interleukin 15</subject><subject>Interleukin-15 - pharmacology</subject><subject>Internal Medicine</subject><subject>K562 Cells</subject><subject>Killer Cells, Natural - drug effects</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - pathology</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Monoclonal antibodies</subject><subject>Oncology</subject><subject>original-article</subject><subject>Peripheral blood</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology</subject><subject>Precursors</subject><subject>Purging</subject><subject>Remission Induction</subject><subject>Toxicity</subject><subject>Transplantation</subject><subject>Transplants</subject><subject>Transplants & 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of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells</title><author>Fei, F ; Lim, M ; George, A A ; Kirzner, J ; Lee, D ; Seeger, R ; Groffen, J ; Abdel-Azim, H ; Heisterkamp, N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c710t-d98349673399d5d6fa9f813a72f17c6b7830cabd030e8f88055611a19630f92c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>13</topic><topic>13/1</topic><topic>13/106</topic><topic>13/31</topic><topic>631/154/51/1844</topic><topic>631/67/1990/283</topic><topic>631/67/580</topic><topic>692/699/67/1990/283/2125</topic><topic>Acute lymphoblastic leukemia</topic><topic>Acute lymphocytic leukemia</topic><topic>Antibodies, Monoclonal - biosynthesis</topic><topic>Antigens</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Autografts</topic><topic>B-Lymphocytes - drug effects</topic><topic>B-Lymphocytes - immunology</topic><topic>B-Lymphocytes - pathology</topic><topic>Bone marrow</topic><topic>Bone Marrow Cells - drug effects</topic><topic>Bone Marrow Cells - immunology</topic><topic>Bone Marrow Cells - pathology</topic><topic>Bone marrow transplantation</topic><topic>Cancer Research</topic><topic>Care and treatment</topic><topic>CD3 antigen</topic><topic>CD3 Complex - genetics</topic><topic>CD3 Complex - metabolism</topic><topic>CD56 antigen</topic><topic>CD56 Antigen - genetics</topic><topic>CD56 Antigen - metabolism</topic><topic>Cell culture</topic><topic>Cell mediated cytotoxicity</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell therapy</topic><topic>Cellular proteins</topic><topic>Chemotherapy</topic><topic>Child</topic><topic>Coculture Techniques</topic><topic>Critical Care Medicine</topic><topic>Cytotoxicity</topic><topic>Cytotoxicity, Immunologic</topic><topic>Development and 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titles)</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fei, F</au><au>Lim, M</au><au>George, A A</au><au>Kirzner, J</au><au>Lee, D</au><au>Seeger, R</au><au>Groffen, J</au><au>Abdel-Azim, H</au><au>Heisterkamp, N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>29</volume><issue>4</issue><spage>788</spage><epage>797</epage><pages>788-797</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) affects hematopoietic development and therefore is associated with immune deficiencies that can be further exacerbated by chemotherapy. It is unclear if and when monoclonal antibodies (mAbs) that stimulate antibody-mediated cellular cytotoxicity (ADCC) can be used for treatment because this depends on the presence of functional effector cells. Here, we used flow cytometry to determine that patient samples at diagnosis, post-induction and relapse contain detectable numbers of CD56+ cells. We were able to selectively expand CD56+ immune effector cells from bone marrow and peripheral blood samples at diagnosis and at various stages of treatment by co-culture with artificial antigen-presenting K562 clone 9.mbIL-21 cells. Amplified CD56+CD3− cells had spontaneous and anti-B cell-activating factor receptor mAb-stimulated ADCC activity against allogeneic ALL cells, which could be further enhanced by IL-15. Importantly, matched CD56+ effector cells also killed autologous ALL cells grown out from leukemia samples of the same patient, through both spontaneous as well as antibody-dependent cellular cytotoxicity. Since autologous cell therapy will not be complicated by graft-versus-host disease, our results show that expanded CD56+ cells could be applied for treatment of pre-B ALL without transplantation, or for purging of bone marrow in the setting of autologous bone marrow transplants.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>25134458</pmid><doi>10.1038/leu.2014.246</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 13 13/1 13/106 13/31 631/154/51/1844 631/67/1990/283 631/67/580 692/699/67/1990/283/2125 Acute lymphoblastic leukemia Acute lymphocytic leukemia Antibodies, Monoclonal - biosynthesis Antigens Antineoplastic Agents - therapeutic use Autografts B-Lymphocytes - drug effects B-Lymphocytes - immunology B-Lymphocytes - pathology Bone marrow Bone Marrow Cells - drug effects Bone Marrow Cells - immunology Bone Marrow Cells - pathology Bone marrow transplantation Cancer Research Care and treatment CD3 antigen CD3 Complex - genetics CD3 Complex - metabolism CD56 antigen CD56 Antigen - genetics CD56 Antigen - metabolism Cell culture Cell mediated cytotoxicity Cell Proliferation - drug effects Cell therapy Cellular proteins Chemotherapy Child Coculture Techniques Critical Care Medicine Cytotoxicity Cytotoxicity, Immunologic Development and progression Diagnosis Drug therapy Effector cells Flow cytometry Gene Expression Genetic aspects Graft-versus-host reaction Health aspects Hematology Hemopoiesis Humans Intensive Interleukin 15 Interleukin-15 - pharmacology Internal Medicine K562 Cells Killer Cells, Natural - drug effects Killer Cells, Natural - immunology Killer Cells, Natural - pathology Leukemia Lymphatic leukemia Lymphocytes Lymphocytes B Medicine Medicine & Public Health Monoclonal antibodies Oncology original-article Peripheral blood Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology Precursors Purging Remission Induction Toxicity Transplantation Transplants Transplants & implants |
title | Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells |
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