NDLI: Comparative assessment of clinically utilized CD20-directed antibodies in chronic lymphocytic leukemia cells reveals divergent NK cell, monocyte, and macrophage properties.

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Comparative assessment of clinically utilized CD20-directed antibodies in chronic lymphocytic leukemia cells reveals divergent NK cell, monocyte, and macrophage properties.

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Comparative assessment of clinically utilized CD20-directed antibodies in chronic lymphocytic leukemia cells reveals divergent NK cell, monocyte, and macrophage properties.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Jarjoura, David Trotta, Rossana Byrd, John C. Tridandapani, Susheela Muthusamy, Natarajan Cheney, Carolyn Rafiq, Sarwish Caligiuri, Michael Mo, Xiaokui Butchar, Jonathan P.
Description	Country affiliation: United States Author Affiliation: Rafiq S ( Integrated Biomedical Science Graduate Program, The Ohio State University, Columbus, OH 43210, USA.)
Abstract	CD20 is a widely validated, B cell-specific target for therapy in B cell malignancies. Rituximab is an anti-CD20 Ab that prolongs survival of chronic lymphocytic leukemia (CLL) patients when combined with chemotherapy. Ofatumumab and GA101 (obinutuzumab) are CD20-directed Abs currently being developed as alternative agents to rituximab in CLL based upon different properties of enhanced direct cell death, NK cell-mediated Ab-dependent cellular cytotoxicity, or complement-dependent cytotoxicity. Despite widespread study, ofatumumab and GA101 have not been compared with each other, nor studied for their interactions with monocytes and macrophages which are critical for the efficacy of anti-CD20 Abs in murine models. In CLL cells, we show that direct cell death and complement-dependent cytotoxicity are greatest with GA101 and ofatumumab, respectively. GA101 promotes enhanced NK cell activation and Ab-dependent cellular cytotoxicity at high Ab concentrations. Ofatumumab elicits superior Ab-dependent cellular phagocytosis with monocyte-derived macrophages. GA101 demonstrated reduced activation of monocytes with diminished pERK, TNF- release, and FcÎ³RIIa recruitment to lipid rafts. These data demonstrate that GA101 and ofatumumab are both superior to rituximab against CLL cells via different mechanisms of potential tumor elimination. These findings bear relevance to potential combination strategies with each of these anti-CD20 Abs in the treatment of CLL.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1202588
Journal	The Journal of Immunology
Issue Number	6
Volume Number	190
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-03-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antibodies, Neoplasm Toxicity Antigens, Cd20 Immunology Drug Delivery Systems Killer Cells, Natural Leukemia, Lymphocytic, Chronic, B-cell Therapy Macrophages Monocytes Therapeutic Use Metabolism Cell Line, Tumor Cytotoxicity Tests, Immunologic Pathology Tumor Cells, Cultured Comparative Study Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Comparative Assessment of Clinically Utilized CD20-directed Antibodies in Chronic Lymphocytic Leukemia Cells Reveals Divergent NK cell, Monocyte and Macrophage Properties

Divergent NK Cell , Monocyte , and Chronic Lymphocytic Leukemia Cells Utilized CD 20-Directed Antibodies in Comparative Assessment of Clinically

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Aberrant NK cell associated marker (CD56 and CD57) expression in chronic lymphocytic leukemia.

NK cell dysfunction in chronic lymphocytic leukemia is associated with loss of the mature cells expressing inhibitory killer cell Ig-like receptors

Comparative assessment of clinically utilized CD20-directed antibodies in chronic lymphocytic leukemia cells reveals divergent NK cell, monocyte, and macrophage properties.

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Comparative Assessment of Clinically Utilized CD20-directed Antibodies in Chronic Lymphocytic Leukemia Cells Reveals Divergent NK cell, Monocyte and Macrophage Properties

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Comparative assessment of clinically utilized CD20-directed antibodies in chronic lymphocytic leukemia cells reveals divergent NK cell, monocyte, and macrophage properties.