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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-\u03b1 release, and Fc\u03b3RIIa 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1202588","type":"journal-article","created":{"date-parts":[[2013,2,16]],"date-time":"2013-02-16T05:53:52Z","timestamp":1360994032000},"page":"2702-2711","source":"Crossref","is-referenced-by-count":85,"title":["Comparative Assessment of Clinically Utilized CD20-Directed Antibodies in Chronic Lymphocytic Leukemia Cells Reveals Divergent NK Cell, Monocyte, and Macrophage Properties"],"prefix":"10.1093","volume":"190","author":[{"given":"Sarwish","family":"Rafiq","sequence":"first","affiliation":[{"name":"Integrated Biomedical Science Graduate Program, The Ohio State University , Columbus, OH 43210"},{"name":"Division of Hematology, Department of Internal Medicine, The Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P","family":"Butchar","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, The Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Cheney","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, The Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokui","family":"Mo","sequence":"additional","affiliation":[{"name":"Center for Biostatistics, The Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Trotta","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, The Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Caligiuri","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, The Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jarjoura","sequence":"additional","affiliation":[{"name":"Center for Biostatistics, The Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susheela","family":"Tridandapani","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, The Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natarajan","family":"Muthusamy","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, The Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Byrd","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, The Ohio State University , Columbus, OH 43210"},{"name":"Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,3,15]]},"reference":[{"key":"2025032406423378300_r1","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.1182\/blood-2010-04-001230","article-title":"The clinical application of monoclonal antibodies in chronic lymphocytic leukemia","volume":"116","author":"Jaglowski","year":"2010","journal-title":"Blood"},{"key":"2025032406423378300_r2","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1053\/j.seminhematol.2010.01.005","article-title":"Rituximab in chronic lymphocytic leukemia","volume":"47","author":"Jaglowski","year":"2010","journal-title":"Semin. 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