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Several mechanisms of target cell killing occur from anti\u2010<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>20 therapy, including complement\u2010dependent cytotoxicity (<jats:styled-content style=\"fixed-case\">CDC<\/jats:styled-content>) cell lysis and antibody\u2010dependent cell\u2010mediated cytotoxicity. Human Fc receptors (FcRs) are required to mediate these functions and are either not present or not cross\u2010reactive in mice and most animal species. In contrast, some nonhuman primates have cross\u2010reactive FcR; however, their cellular expression and function may differ from humans. Therefore, we tested bone marrow\u2010liver\u2010thymus (<jats:styled-content style=\"fixed-case\">BLT<\/jats:styled-content>) humanized mice to determine if they could recapitulate the pharmacokinetics (PKs), pharmacodynamics, and potential toxicities of ofatumumab, for which <jats:styled-content style=\"fixed-case\">CDC<\/jats:styled-content> is the predominant mechanism of action. Ofatumumab\u2010treated <jats:styled-content style=\"fixed-case\">BLT<\/jats:styled-content> mice depleted B cells in a dose\u2010dependent manner in all tissues sampled and recapitulated the PKs observed in humans, suggesting that <jats:styled-content style=\"fixed-case\">BLT<\/jats:styled-content> mice can mediate the <jats:styled-content style=\"fixed-case\">CDC<\/jats:styled-content> effector mechanism associated with biological drug products.<\/jats:p>","DOI":"10.1111\/cts.12613","type":"journal-article","created":{"date-parts":[[2019,2,9]],"date-time":"2019-02-09T09:18:12Z","timestamp":1549703892000},"page":"283-290","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Evaluation of the Ability of Immune Humanized Mice to Demonstrate <scp>CD<\/scp>20\u2010Specific Cytotoxicity Induced by\u00a0Ofatumumab"],"prefix":"10.1111","volume":"12","author":[{"given":"Kenrick M.","family":"Semple","sequence":"first","affiliation":[{"name":"Division of Applied Regulatory Sciences Office of Translational Sciences Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"},{"name":"Division of Gastroenterology and Inborn Errors Products Office of New Drugs Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos M.","family":"Gonzal\u00e9z","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Sciences Office of Translational Sciences Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"},{"name":"Division of Drug Quality I Office of Compliance Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Zarr","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Analysis II Office of Testing and Research Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"},{"name":"NextCure, Inc.  Beltsville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 R.","family":"Austin","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Sciences Office of Translational Sciences Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Sciences Office of Translational Sciences Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina E.","family":"Howard","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Sciences Office of Translational Sciences Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,27]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1431"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.cji.0000203081.43235.d7"},{"key":"e_1_2_11_3_1","first-page":"1002","article-title":"Rituximab\u2010mediated antibody\u2010dependent cellular cytotoxicity against neoplastic B cells is stimulated strongly by interleukin\u20102","volume":"88","author":"Golay J.","year":"2003","journal-title":"Haematologica"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.12.3900"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.3280"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.06.151"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-01-0039"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2009.139"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2015.06.009"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyt022"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08193.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/13.12.1551"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.1.180"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12952"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01156-13"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.362"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.12.3383"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-010-0905-2"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcts.12613","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12613","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.12613","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12613","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T08:55:22Z","timestamp":1694336122000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.12613"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,27]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1111\/cts.12613"],"URL":"https:\/\/doi.org\/10.1111\/cts.12613","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,27]]},"assertion":[{"value":"2018-10-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}