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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Veröffentlicht in:Leukemia 2015-04, Vol.29 (4), p.788-797
Hauptverfasser: Fei, F, Lim, M, George, A A, Kirzner, J, Lee, D, Seeger, R, Groffen, J, Abdel-Azim, H, Heisterkamp, N
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container_end_page 797
container_issue 4
container_start_page 788
container_title Leukemia
container_volume 29
creator Fei, F
Lim, M
George, A A
Kirzner, J
Lee, D
Seeger, R
Groffen, J
Abdel-Azim, H
Heisterkamp, N
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. 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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. 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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 &amp; implants</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFksuL1TAUxosoznV051oKgriw17yax0a4Xp8w4EbXITdNezOmTU3Swf73ptyZoSODkkUg53e-c86XUxTPIdhCgPlbZ6YtApBsEaEPig0kjFZ1XcOHxQZwzioqEDkrnsR4CcASpI-LM1RDTEjNN8W4n5NP_rfVNs2lb8v9h5pWo4822StTurkfj17PycRSdcoOMZVqSt75zk-xfF9p41w5BqOnEH0olZ7STdbBqZisLnODP01vVbmw8WnxqFUummfX93nx49PH7_sv1cW3z1_3u4tKMwhS1QiOiaAMYyGauqGtEi2HWDHUQqbpgXEMtDo0AAPDW85BXVMIFRQUg1Ygjc-LdyfdcTr0ptFmSEE5OQbbqzBLr6y8GxnsUXb-ShKMCatZFnh9LRD8r8nEJHsblxHUYPLsElKeydwlyejLv9BLP4UhjycRxpBmswH4FwUpQ4AhvqY65Yy0Q-tzd3opLXcEAgEIEkvF7T1UPk12WvvBtDa_30l4tUo4GuXSMXo3JeuHKHcUAgQwE-x_4FrxzQnUwccYTHvrLQRy2UyZP14umynzZmb8xfo_buGbVcxAdQJiDg2dCSt77hP8A6Kj6zs</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Fei, F</creator><creator>Lim, M</creator><creator>George, A A</creator><creator>Kirzner, J</creator><creator>Lee, D</creator><creator>Seeger, R</creator><creator>Groffen, J</creator><creator>Abdel-Azim, H</creator><creator>Heisterkamp, N</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>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>5PM</scope></search><sort><creationdate>20150401</creationdate><title>Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells</title><author>Fei, F ; 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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.</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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