title: Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells.
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.
authors.affiliation: 1] Section of Molecular Carcinogenesis, Los Angeles, CA, USA [2] Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Fei
authors.affiliation: 1] Section of Molecular Carcinogenesis, Los Angeles, CA, USA [2] Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lim
authors.affiliation: Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: George
authors.affiliation: Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kirzner
authors.affiliation: Division of Pediatrics, Cell Therapy Section, MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: Lee
authors.affiliation: Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Seeger
authors.affiliation: 1] Section of Molecular Carcinogenesis, Los Angeles, CA, USA [2] Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA, USA [3] Leukemia and Lymphoma Program, Norris Comprehensive Cancer Center, University of Southern California, California, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Groffen
authors.affiliation: Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Abdel-Azim
authors.affiliation: 1] Section of Molecular Carcinogenesis, Los Angeles, CA, USA [2] Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA, USA [3] Leukemia and Lymphoma Program, Norris Comprehensive Cancer Center, University of Southern California, California, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Heisterkamp
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D019002:CD56 Antigen / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D012074:Remission Induction
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017252:CD3 Complex; D019002:CD56 Antigen; C569274:IL15 protein, human; D019409:Interleukin-15; C522918:NCAM1 protein, human