{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T07:17:20Z","timestamp":1773731840269,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2019,8,24]],"date-time":"2019-08-24T00:00:00Z","timestamp":1566604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Polatuzumab vedotin is an antibody\u2013drug conjugate (ADC) being developed for non\u2010Hodgkin's lymphoma. It contains a humanized anti\u2010CD79b IgG1 monoclonal antibody linked to monomethyl auristatin E (MMAE), an anti\u2010mitotic agent. Polatuzumab vedotin binds to human CD79b only. Therefore, a surrogate ADC that binds to cynomolgus monkey CD79b was used to determine CD79b\u2010mediated pharmacological effects in the monkey and to enable first\u2010in\u2010human clinical trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Polatuzumab vedotin, the surrogate ADC, and the corresponding antibodies were evaluated in different assays in vitro and in animals. In vitro assessments included binding to peripheral blood mononuclear cells from different species, binding to a human and monkey CD79b\u2010expressing cell line, binding to human Fc\u03b3 receptors, and stability in plasma across species. In vivo, ADCs were assessed for anti\u2010tumour activity in mice, pharmacokinetics\/pharmacodynamics in monkeys, and toxicity in rats and monkeys.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Polatuzumab vedotin and surrogate ADC bind with similar affinity to human and cynomolgus monkey B cells, respectively. Comparable in vitro plasma stability, in vivo anti\u2010tumour activity, and mouse pharmacokinetics were also observed between the surrogate ADC and polatuzumab vedotin. In monkeys, only the surrogate ADC showed B\u2010cell depletion and B\u2010cell\u2010mediated drug disposition, but both ADCs showed similar MMAE\u2010driven myelotoxicity, as expected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The suitability of the surrogate ADC for evaluation of CD79b\u2010dependent pharmacology was demonstrated, and anti\u2010tumour activity, pharmacokinetics\/pharmacodynamics, and toxicity data with both ADCs supported the entry of polatuzumab vedotin into clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14784","type":"journal-article","created":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T02:08:36Z","timestamp":1562206116000},"page":"3805-3818","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Evaluation and use of an anti\u2010cynomolgus monkey CD79b surrogate antibody\u2013drug conjugate to enable clinical development of polatuzumab vedotin"],"prefix":"10.1111","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8914-3021","authenticated-orcid":false,"given":"Dongwei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacokinetic and Pharmacodynamic Sciences Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Safety Assessment Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randall C.","family":"Dere","sequence":"additional","affiliation":[{"name":"Department of BioAnalytical Sciences Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Translational Oncology Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shang\u2010Fan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Translational Oncology Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franklin K.","family":"Fuh","sequence":"additional","affiliation":[{"name":"Department of OMNI\u2010Biomarker Development Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine R.","family":"Kozak","sequence":"additional","affiliation":[{"name":"Department of Biochemical and Cellular Pharmacology Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of BioAnalytical Sciences Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Bumbaca Yadav","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetic and Pharmacodynamic Sciences Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Nazzal","sequence":"additional","affiliation":[{"name":"Department of BioAnalytical Sciences Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitry","family":"Danilenko","sequence":"additional","affiliation":[{"name":"Department of Safety Assessment Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Ann T.","family":"Go","sequence":"additional","affiliation":[{"name":"Department of Translational Oncology Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marna","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine MedImmune  Gaithersburg MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew G.","family":"Polson","sequence":"additional","affiliation":[{"name":"Department of Translational Oncology Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten Achilles","family":"Poon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Ultragenyx Pharmaceutical, Inc.  Novato CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saileta","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetic and Pharmacodynamic Sciences Genentech, Inc.  South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13882"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.268"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2009.09.014"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581809337262"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-2391"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-293050"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.19941"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2004.06.007"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4892(03)00083-3"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.3.1.13799"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.435"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-205500"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt832"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2004.1.221"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13697"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.13.38"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4274(92)90204-W"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(04)01490-1"},{"key":"e_1_2_11_21_1","unstructured":"Institute of Laboratory Animal Research National Research Council(1996).Guide for the Care and Use of Laboratory Animals. Available at:https:\/\/grants.nih.gov\/grants\/olaw\/Guide-for-the-Care-and-Use-of-Laboratory-Animals.pdf"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc300491k"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2005.12.041"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002800050995"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(80)90515-1"},{"key":"e_1_2_11_27_1","unstructured":"NCT01290549(2017).A study of escalating doses of polatuzumab vedotin in participants with relapsed or refractory B\u2010cell non\u2010Hodgkins lymphoma and chronic lymphocytic leukemia and polatuzumab vedotin in combination with rituximab in participants with relapsed or refractory B\u2010cell non\u2010Hodgkins lymphoma. ClinicalTrials.gov Identifier: NCT01290549."},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)70128-2"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2010.529206"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2250"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-066704"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/laban.1217"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2015.01.014"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510026200"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1191\/096032700678815765"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-09-0369"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14784","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.14784","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14784","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T17:42:42Z","timestamp":1694194962000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.14784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,24]]},"references-count":35,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1111\/bph.14784"],"URL":"https:\/\/doi.org\/10.1111\/bph.14784","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,24]]},"assertion":[{"value":"2018-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}