{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:02:38Z","timestamp":1794009758609,"version":"4.8.0"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T00:00:00Z","timestamp":1551916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:p>\n                    Tisagenlecleucel is a chimeric antigen receptor\u2013T cell therapy that facilitates the killing of CD19\n                    <jats:sup>+<\/jats:sup>\n                    B cells. A model was developed for the kinetics of tisagenlecleucel and the impact of therapies for treating cytokine release syndrome (tocilizumab and corticosteroids) on expansion. Data from two phase II studies in pediatric and young adult relapsed\/refractory B cell acute lymphoblastic leukemia were pooled to evaluate this model and evaluate extrinsic and intrinsic factors that may impact the extent of tisagenlecleucel expansion. The doubling time, initial decline half\u2010life, and terminal half\u2010life for tisagenlecleucel were 0.78, 4.3, and 220\u00a0days, respectively. No impact of tocilizumab or corticosteroids on the expansion rate was observed. This work represents the first mixed\u2010effect model\u2010based analysis of chimeric antigen receptor\u2013T cell therapy and may be clinically impactful as future studies examine prophylactic interventions in patients at risk of higher grade cytokine release syndrome and the effects of these interventions on chimeric antigen receptor\u2013T cell expansion.\n                  <\/jats:p>","DOI":"10.1002\/psp4.12388","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T00:09:03Z","timestamp":1552003743000},"page":"285-295","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":131,"title":["Tisagenlecleucel Model\u2010Based Cellular Kinetic Analysis of Chimeric Antigen Receptor\u2013T Cells"],"prefix":"10.1002","volume":"8","author":[{"given":"Andrew M.","family":"Stein","sequence":"first","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan A.","family":"Grupp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Division of Oncology Center for Childhood Cancer Research and Cancer Immunotherapy Program Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Levine","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor Michigan USA"},{"name":"Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore W.","family":"Laetsch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The University of Texas Southwestern Medical Center  Dallas Texas USA"},{"name":"Pauline Allen Gill Center for Cancer and Blood Disorders Children's Health  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Pulsipher","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology, and Blood and Marrow Transplantation Children's Hospital Los Angeles Keck School of Medicine of University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Boyer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Internal Medicine University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5690-0855","authenticated-orcid":false,"given":"Keith J.","family":"August","sequence":"additional","affiliation":[{"name":"Children's Mercy Hospital Kansas City  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce L.","family":"Levine","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Tomassian","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sweta","family":"Shah","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mimi","family":"Leung","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pai\u2010Hsi","family":"Huang","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Awasthi","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen Thudium","family":"Mueller","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Wood","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl H.","family":"June","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,7]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215134"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2017.07.030"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709866"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2012.12.025"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.22.10663-10669.2001"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002842"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-786129"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0028"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-84-3-304"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1996.tb08306.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.34.15_suppl.3011"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.007"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.10.4969"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac5415"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003761"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-05-552729"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2017.07.028"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-150680"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.403"},{"key":"e_1_2_10_20_1","unstructured":"Final report pharmacometric analysis\u2013Kymriah (tisagenlecleucel). <https:\/\/www.fda.gov\/BiologicsBloodVaccines\/CellularGeneTherapyProducts\/ApprovedProducts\/ucm573706.htm>. Accessed September 25 2018."},{"key":"e_1_2_10_21_1","unstructured":"Pharmacometric review\u2013Yescarta (axicabtagene ciloleucel). <https:\/\/www.fda.gov\/BiologicsBloodVaccines\/CellularGeneTherapyProducts\/ApprovedProducts\/ucm581222.htm>. Accessed September 25 2018."},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00352"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407222"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V128.22.220.220"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpsp4.12388","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.12388","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.12388","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.12388","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T17:51:34Z","timestamp":1694368294000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.12388"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,7]]},"references-count":24,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1002\/psp4.12388"],"URL":"https:\/\/doi.org\/10.1002\/psp4.12388","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.735289343.793559715","asserted-by":"object"}]},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,7]]},"assertion":[{"value":"2018-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}