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Recent observations have revealed significant pharmacological effects of CD19 CAR\u2010T cells in patients with systemic lupus erythematosus (SLE), suggesting promising applications in other autoimmune conditions. Consequently, as of December 2024, there are 116 different clinical trials evaluating CAR\u2010T cells against autoimmune conditions. While the field is starting to understand the overall pharmacological actions of CAR\u2010T cells in autoimmune diseases, the dose\u2010exposure\u2010response relationship remains inadequately characterized due to limited clinical data. To address these uncertainties, we have developed a Quantitative Systems Pharmacology (QSP) model using short\u2010term limited clinical data of anti\u2010CD19 CAR\u2010Ts in autoimmune disease patients (<jats:italic>n<\/jats:italic>\u2009=\u20095), followed by a model qualification step utilizing an external dataset (<jats:italic>n<\/jats:italic>\u2009=\u200913). The developed QSP model integrated and effectively characterized the (1) cellular kinetics of different immunophenotypic population of CAR\u2010T cells, (2) impact of lymphodepletion chemotherapy on host immune cells, (3) CAR\u2010mediated elimination of CD19+ B\u2010cells and (4) dynamic changes in disease surrogate biomarkers and its relationship with clinical score. The key pharmacological biomarkers which were incorporated within the QSP model included anti double stranded DNA (anti\u2010dsDNA) antibodies, proteinuria, C3 protein and IFN\u2010alpha. Later, a linear regression analysis\u2010based relationship was developed between continuous disease biomarkers and the categorical SLE disease activity index (SLE\u2010DAI) determined by the investigators offering a predictive framework for disease progression in SLE patients. This proposed QSP model holds potential to elucidate quantitative pharmacology and expedite clinical advancement of autologous and allogeneic cell therapies in autoimmune diseases.<\/jats:p>","DOI":"10.1111\/cts.70146","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T07:45:16Z","timestamp":1739346316000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mechanistic Evaluation of Anti\u2010<scp>CD19 CAR<\/scp>\u2010T Cell Therapy Repurposed in Systemic Lupus Erythematosus Using a Quantitative Systems Pharmacology Model"],"prefix":"10.1111","volume":"18","author":[{"given":"Hyunseo","family":"Park","sequence":"first","affiliation":[{"name":"Cell Therapy Clinical Pharmacology and Modeling Precision and Translational Medicine Takeda Pharmaceuticals  Cambridge Massachusetts USA"},{"name":"Department of Pharmaceutical Sciences College of Pharmacy, University of Tennessee Health Sciences Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh M.","family":"Mugundu","sequence":"additional","affiliation":[{"name":"Cell Therapy Clinical Pharmacology and Modeling Precision and Translational Medicine Takeda Pharmaceuticals  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aman P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Cell Therapy Clinical Pharmacology and Modeling Precision and Translational Medicine Takeda Pharmaceuticals  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.927153"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01126-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02716-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199406303302608"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218272"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2017.03.033"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12196268"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav1648"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-189673"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2308917"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02017-5"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8090963"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-006-9035-z"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/js980171q"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.02.140"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13009"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12598"},{"key":"e_1_2_9_19_1","first-page":"413","article-title":"Quantitative Analysis of CD79b, CD5 and CD19 in Mature B\u2010Cell Lymphoproliferative Disorders","volume":"84","author":"Cabezudo E.","year":"1999","journal-title":"Haematologica"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.11.1923"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adf1426"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2021-000499"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V67.6.1600.1600"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-09-3740"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2021.03.007"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0549-5"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coisb.2019.10.002"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-700336"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00551-09"},{"key":"e_1_2_9_30_1","first-page":"21","article-title":"Decreased Synthesis of the Third Component of Complement (C3) in Hypocomplementemic Systemic Lupus Erythematosus","volume":"11","author":"Sliwinski A. 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