{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:50:29Z","timestamp":1791521429853,"version":"4.3.4"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"\n Background<\/jats:title>\n CD19-targeting chimeric antigen receptor (CAR)-T cells have demonstrated great efficacy in treating relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL). Despite the high objective response rate of CAR-T cell therapy, high-risk adverse event of cytokine-release syndrome occur unexpectedly.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n As living gene-modified cells, CAR-T cells exhibit unique kinetics. This study aimed to explore the relationship between CAR-T therapy-related CRS and the kinetics of CAR-T cells.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this study, data for 2184 CAR-transgene copies from 131\u00a0B-ALL patients treated with IL-6 knockdown CD19-targeting CAR-T cells were included to characterize the cellular kinetics using a nonlinear mixed-effects (NLME) model. The extrinsic and intrinsic factors that may impact the kinetics of CAR-T cells were also evaluated.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The CD4\n +<\/jats:sup>\n \/CD8\n +<\/jats:sup>\n ratio of CAR-T cell products was shown to be significantly positively correlated with T\n max<\/jats:sub>\n , suggesting that a higher CD4\n +<\/jats:sup>\n \/CD8\n +<\/jats:sup>\n ratio may lead to a delay in reaching the maximum expansion, while other candidate covariates including tumor burden, CAR-T doses and comedication were not significantly associated with the kinetics of CAR-T cells. The estimated values of the cellular kinetic parameters C\n max<\/jats:sub>\n , T\n max<\/jats:sub>\n and Fold\n x<\/jats:sub>\n were 4.696 \u00d7 10\n 4<\/jats:sup>\n copies\/\u03bcg, 13.0 days, and 127.5, respectively. The estimated AUC\n 0-28d<\/jats:sub>\n and AUC\n 0-90d<\/jats:sub>\n accounted for only 13.0% and 18.5% of AUC\n 0-inf<\/jats:sub>\n , respectively, indicating that there was long-term persistence of memory CAR-T cells\n in vivo<\/jats:italic>\n . In addition, the incidence of CRS was investigated to be correlated with the early kinetics of CAR-T cells, and the optimal cutoff values of C\n max<\/jats:sub>\n and AUC\n 0-28d<\/jats:sub>\n for severe CRS were 6.951 \u00d7 10\n 4<\/jats:sup>\n copies\/\u03bcg and 4.962 \u00d7 10\n 5<\/jats:sup>\n copies\/\u03bcg \u00d7 days, respectively.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2026.1878984","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:27:10Z","timestamp":1791520030000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Population cellular kinetics and exposure-CSR analysis of CAR-T cells in Chinese patients with relapsed\/refractory B-ALL"],"prefix":"10.3389","volume":"17","author":[{"given":"Yicong","family":"Bian","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Soochow University","place":["Suzhou, 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Soochow University","place":["Suzhou, China"]},{"name":"Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]},{"name":"National Institution of Drug Clinical Trial, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]},{"name":"Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd","place":["Shanghai, 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