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<p>Despite the success of CAR T therapy in non-Hodgkin lymphoma (NHL), recurrence remains challenging. Previously, we showed that ex vivo priming with decitabine (DAC) enhances CAR T persistence and efficacy. Here, we report on an open-label non-randomised phase I/II trial (NCT04697940) evaluating DAC-primed CD19/CD20 dual-targeted CAR T cells (dCAR T) in 23 patients with relapsed or refractory NHL. Primary endpoints are safety and dose-toxicity for phase I, and overall response rate and complete response rate (CRR) for phase II. Secondary endpoints include progression-free survival (PFS), overall survival, and duration of response. This trial has met pre-specified endpoints. Treatment is well tolerated and achieves durable responses, with an 87% CRR and a 2-year PFS of 77% (median follow-up, 24.3 months). Compared with historically unmodified CAR T cohorts, dCAR T cells exhibited robust in vivo expansion and sustained persistence. Single-cell sequencing indicates that DAC priming enriches for memory-like progenitors, which maintain cytotoxic and memory signatures, and upregulates genes associated with T cell fitness and engagement of endogenous immunity. These data establish DAC-priming as a clinically feasible epigenetic reprogramming strategy enhanceing CAR T durability and efficacy, offering a generalizable paradigm for engineered cell therapies in malignant tumors.</p>

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Demethylation-primed tandem CD19/CD20 CAR T cells in relapsed/refractory B-cell lymphoma: a phase I/II trial

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月15日

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  • Chunmeng Wang,
  • Yelei Guo,
  • Fuxin Han,
  • Yipeng Zhang,
  • Chun Liu,
  • Zhiqiang Wu,
  • Chuan Tong,
  • Qingming Yang,
  • Yuting Lu,
  • Yadi Zhong,
  • Jinhong Shi,
  • Jianshu Wei,
  • Yajing Zhang,
  • Yang Liu,
  • Yao Wang,
  • Weidong Han

摘要

Despite the success of CAR T therapy in non-Hodgkin lymphoma (NHL), recurrence remains challenging. Previously, we showed that ex vivo priming with decitabine (DAC) enhances CAR T persistence and efficacy. Here, we report on an open-label non-randomised phase I/II trial (NCT04697940) evaluating DAC-primed CD19/CD20 dual-targeted CAR T cells (dCAR T) in 23 patients with relapsed or refractory NHL. Primary endpoints are safety and dose-toxicity for phase I, and overall response rate and complete response rate (CRR) for phase II. Secondary endpoints include progression-free survival (PFS), overall survival, and duration of response. This trial has met pre-specified endpoints. Treatment is well tolerated and achieves durable responses, with an 87% CRR and a 2-year PFS of 77% (median follow-up, 24.3 months). Compared with historically unmodified CAR T cohorts, dCAR T cells exhibited robust in vivo expansion and sustained persistence. Single-cell sequencing indicates that DAC priming enriches for memory-like progenitors, which maintain cytotoxic and memory signatures, and upregulates genes associated with T cell fitness and engagement of endogenous immunity. These data establish DAC-priming as a clinically feasible epigenetic reprogramming strategy enhanceing CAR T durability and efficacy, offering a generalizable paradigm for engineered cell therapies in malignant tumors.