文章：

供者来源的经Sleeping Beauty转座子工程化改造的CARCIK-CD19细胞治疗异基因移植后复发的急性淋巴细胞白血病

Donor-derived CARCIK-CD19 cells engineered with Sleeping Beauty transposon in acute lymphoblastic leukemia relapsed after allogeneic transplantation

原文发布日期：2025-04-03

DOI: 10.1038/s41408-025-01260-6

类型: Article

开放获取: 是

英文摘要：

Non-viral engineering can ease CAR-T cell production and reduce regulatory and cost requirements. We utilized Sleeping Beauty transposon to engineer donor-derived anti-CD19.CD28.OX40.CD3zeta T cells differentiated in cytokine-induced killer (CARCIK-CD19) for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients relapsed after allogeneic hematopoietic stem cell transplantation (alloHSCT). We report the results of CARCIK-CD19 observed in 36 patients (4 children and 32 adults) treated according to the final recommended dose. Cytokine release syndrome of grade 2 or lower occurred in 15 patients, ICANS grade 2 in 1 patient, and late-onset peripheral neurotoxicity of grade 3 in 2 patients. GVHD never occurred after treatment with allogeneic CARCIK-CD19. Complete remission was achieved by 30 out of 36 patients (83.3%), with MRD negativity in 89% of responders. With a median follow-up of 2.2 years, the 1-year overall survival was 57.0%, and event-free survival was 32.0%. The median duration of response at 1 year was 38.6%. CAR-T cells expanded rapidly after infusion and remained detectable for over 2 years. Integration site analysis after infusion showed a high clonal diversity. These data demonstrated that SB-engineered CAR-T cells are safe and induce durable remission in heavily pretreated patients with BCP-ALL relapsed after alloHSCT. Trial registration: The phase 1/2 and phase II trials are registered at www.clinicaltrials.gov as NCT#03389035 and NCT#05252403.
 

摘要翻译： 

非病毒工程可以简化CAR-T细胞的生产并降低监管和成本要求。我们利用Sleeping Beauty转座子改造供体来源的抗CD19.CD28.OX40.CD3ζ T细胞，使其在细胞因子诱导的杀伤细胞（CARCIK-CD19）中分化，用于治疗异基因造血干细胞移植（alloHSCT）后复发的B细胞前体急性淋巴细胞白血病（BCP-ALL）患者。我们报告了36例患者（4例儿童和32例成人）按最终推荐剂量治疗后的CARCIK-CD19观察结果：15例患者出现2级或更低的细胞因子释放综合征，1例患者出现2级免疫效应细胞相关神经毒性综合征（ICANS），2例患者出现3级迟发性周围神经毒性。异基因CARCIK-CD19治疗后未发生移植物抗宿主病（GVHD）。36例患者中30例（83.3%）获得完全缓解，应答者中89%达到微小残留病（MRD）阴性。中位随访2.2年，1年总生存率为57.0%，无事件生存率为32.0%。1年时中位缓解持续时间为38.6%。CAR-T细胞输注后迅速扩增，并可持续检测超过2年。输注后整合位点分析显示高度克隆多样性。这些数据表明，SB工程化的CAR-T细胞安全性良好，能在异基因造血干细胞移植后复发且经过多重治疗的BCP-ALL患者中诱导持久缓解。试验注册：1/2期和II期试验已在www.clinicaltrials.gov注册，编号为NCT#03389035和NCT#05252403。

原文链接：

Donor-derived CARCIK-CD19 cells engineered with Sleeping Beauty transposon in acute lymphoblastic leukemia relapsed after allogeneic transplantation