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
Hauptverfasser: Weitzman, James, Betancur, Monica, Boissel, Laurent, Rabinowitz, Arthur P., Klein, Andreas, Klingemann, Hans
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container_end_page 1368
container_issue 8
container_start_page 1361
container_title Leukemia & lymphoma
container_volume 50
creator Weitzman, James
Betancur, Monica
Boissel, Laurent
Rabinowitz, Arthur P.
Klein, Andreas
Klingemann, Hans
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.
doi_str_mv 10.1080/10428190903026500
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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. 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1029-2403
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source MEDLINE; Taylor & Francis Medical Library - CRKN; Taylor & Francis Journals Complete
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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