{
  "abstract": "Background: 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.\n\nObjective: 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.\n\nMethods: In this study, data for 2184 CAR-transgene copies from 131 B-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.\n\nResults: The CD4 ⁺ /CD8 ⁺ ratio of CAR-T cell products was shown to be significantly positively correlated with T max , suggesting that a higher CD4 ⁺ /CD8 ⁺ 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 max , T max and Fold x were 4.696 × 10 ⁴ copies/μg, 13.0 days, and 127.5, respectively. The estimated AUC 0-28d and AUC 0-90d accounted for only 13.0% and 18.5% of AUC 0-inf , respectively, indicating that there was long-term persistence of memory CAR-T cells in vivo . 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 max and AUC 0-28d for severe CRS were 6.951 × 10 ⁴ copies/μg and 4.962 × 10 ⁵ copies/μg × days, respectively.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacy, The First Affiliated Hospital of Soochow University , ,",
    "Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd , ,",
    "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yicong Bian"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinjie Yuan"
    },
    {
      "affs": [
        0
      ],
      "name": "Chenrong Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaijie Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ling Xue"
    },
    {
      "affs": [
        0
      ],
      "name": "Fan Xia"
    },
    {
      "affs": [
        1
      ],
      "name": "Liqing Kang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Hua Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Lei Yu"
    },
    {
      "affs": [
        2
      ],
      "name": "Depei Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Liyan Miao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/en0t0v32cqw9c.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1878984",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690635/?tool=EBI",
  "id": "en0t0v32cqw9c",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13690635",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7221176064",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690635/pdf/?tool=EBI",
  "pmcid": "PMC13690635",
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/en0t0v32cqw9c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:59Z",
      "native_id": "PMC:PMC13690635",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13690635"
    },
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1878984",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1878984/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "Population cellular kinetics and exposure-CSR analysis of CAR-T cells in Chinese patients with relapsed/refractory B-ALL",
  "title_text": "Population cellular kinetics and exposure-CSR analysis of CAR-T cells in Chinese patients with relapsed/refractory B-ALL",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/en0t0v32cqw9c",
  "venue": "Frontiers in pharmacology",
  "versions": []
}