肿瘤细胞治疗研究
英文原题：Donor-derived CD19-targeted CAR-NK cells induce complete remission in a child with relapsed B-ALL after failure of blinatumomab and autologous CD19-targeted CAR-T.
复发仍是儿童 B 细胞急性淋巴细胞白血病（B-ALL）治疗失败和死亡的主要原因。
复发仍是儿童B细胞急性淋巴细胞白血病（B-ALL）治疗失败和死亡的主要原因。对于对贝林妥欧单抗及CAR-T（CAR-T）细胞疗法耐药的患者，亟需新的治疗方法。CAR自然杀伤（NK）细胞因抗肿瘤活性增强且不良事件发生率低，已成为新型癌症免疫疗法的有前景候选方案。然而，CAR-NK细胞治疗儿童复发/难治性B-ALL的疗效数据仍缺乏。我们报告一例棘手病例：一名男童在贝林妥欧单抗治疗后B-ALL复发，对自体靶向CD19的CAR-T细胞疗法及米托蒽醌方案再诱导化疗均无应答。接受供者来源的靶向CD19 CAR-NK细胞输注后，患者达到完全缓解，并发生3级免疫效应细胞相关神经毒性综合征（ICANS），经及时治疗后完全控制。随后患者接受同一供者来源的造血干细胞移植（HSCT），移植后一年仍维持完全缓解。本病例表明，尽管发生了可管理的ICANS，CAR-NK细胞疗法仍可作为桥接HSCT的治疗手段，用于儿童复发/难治性B-ALL。
Relapse remains the primary cause of treatment failure and death in pediatric B-cell acute lymphoblastic leukemia (B-ALL). Novel therapeutic approaches are imperative for those who are refractory to blinatumomab and chimeric antigen receptor T (CAR-T) cell therapy. CAR-natural killer (NK) cells have emerged as promising candidates for novel cancer immunotherapies, with enhanced antitumor activity and low rates of adverse events. However, data on the efficacy of CAR-NK cells for treating pediatric relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) are lacking.We report a challenging case of a boy with relapsed B-ALL after blinatumomab who failed to respond to autologous CD19-targeted CAR-T cell therapy and mitoxantrone-based reinduction chemotherapy. The patient achieved a complete remission after donor-derived CD19-targeted CAR-NK cell infusion, experiencing a grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), which was completely controlled by timely treatment. Then, the patient received the same donor-derived hematopoietic stem cell transplantation (HSCT) and remains in complete remission for a year post-HSCT.Our case provides an example of the utility of CAR-NK cell therapy as a bridge to HSCT in treating pediatric R/R B-ALL, despite the occurrence of ICANS as a manageable toxicity.
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