肿瘤细胞治疗研究
英文原题：A Phase 2, Open-Label, Multicenter Study of the Safety and Efficacy of TAK-007 in Adult Patients with Relapsed/Refractory B-cell Non-Hodgkin Lymphoma.
不良事件可控，细胞因子释放综合征限于 1-2 级（11.5%）。
在复发/难治性大 B 细胞淋巴瘤（LBCL）中，CAR-NK 疗法相较 CAR-T 疗法具有潜在优势，包括现货型供应和可规模化生产。我们开展了一项 II 期研究，在26例经多线治疗的复发/难治性 B 细胞非霍奇金淋巴瘤（NHL）患者中评估单次给药 TAK-007 的疗效。TAK-007 是一种冷冻保存、来源于脐带血、现货型的 CD19 CAR-NK 细胞疗法。不良事件可控，细胞因子释放综合征均为1–2级，发生率为11.5%。接受 TAK-007（8×10⁸个活的 CD19 CAR 阳性 NK 细胞；n=14）治疗者的总缓解率为60.9%（95% CI：38.5–80.3）。在 LBCL（n=10）和惰性 NHL（n=7）扩展队列中，中位无进展生存期分别为2.0个月（95% CI：0.99–3.58）和5.6个月（95% CI：1.05–8.57）。患者获得了深度分子应答，包括循环肿瘤 DNA（ctDNA）转阴。并非所有 TAK-007 产品均能诱发临床应答；单细胞 RNA 测序显示，在诱发应答的产品中 NK 细胞增殖相关特征富集，而未诱发应答的产品中 NK-CD56^dim 细胞富集，这些特征或可用于指导产品选择。
In relapsed/refractory large B-cell lymphoma (LBCL), chimeric antigen receptor (CAR)-natural killer (NK) cell therapies offer potential advantages over CAR-T-cell therapies, including off-the-shelf availability and scalable manufacturing. We performed a phase 2 study of single-dose TAK-007, a cryopreserved, cord blood-derived, off-the-shelf CD19 CAR-NK cell therapy, in 26 heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Adverse events were manageable, with limited grade 1-2 cytokine release syndrome (11.5%). Overall response rate with TAK-007 800 x106 CD19 CAR+ viable NK cells (n=14) was 60.9% (95% CI: 38.5-80.3). Median progression-free survival was 2.0 months (95% CI: 0.99-3.58) in LBCL (n=10) and 5.6 months (95% CI: 1.05-8.57) in indolent NHL (n=7) expansion cohorts. Deep molecular responses, including ctDNA-negative responses, were achieved. Not all TAK-007 products elicited clinical responses; single cell RNA-sequencing showed NK proliferating and NK-CD56dim cell enrichment in TAK-007 products eliciting/not eliciting responses, respectively, which could inform product selection.
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