Blood:采用CD19/22 CAR T细胞治疗儿童和年轻成人B-ALL

2022-08-11 MedSci原创 MedSci原创

总队列的完全缓解(CR)率为60%(12/20),CAR初治患者队列的CR率为71.4%(10/14)

单抗原靶向嵌合抗原受体(CAR)T细胞的缓解持久性受抗原调节的限制,这可通过联合靶向来克服。基于在B细胞急性淋巴细胞白血病(B-ALL)中靶向CD19和CD22的经验,Shalabi等研究人员进行了一项新的小鼠干细胞病毒(MSCV)-CD19/CD22-4-1BB 二价CAR T细胞(CD19.22.BBz)用于儿童和青年B细胞恶性肿瘤患者的1期剂量递增性研究。

该研究的主要终点是毒性和明确剂量。次要终点包括缓解率和无复发生存率。相关的生物学研究包括实验室研究、CAR T细胞扩增和细胞因子分析。


无复发生存率和总生存率

共招募了20位B-ALL患者,年龄在5.4岁到34.6岁,均接受了CD19.22.BBz治疗。总队列的完全缓解(CR)率为60%(12/20),CAR初治患者队列的CR率为71.4%(10/14)。10位(50%)患者经历了细胞因子释放综合征(CRS),其中3例(15%)是3级及以上的CRS;只有1位患者经历了神经毒性(3级)。获得完全缓解的患者的6个月和12个月无复发生存率分别是80.8%和57.7%。

与EF1a-CD22.BBz相比,MSCV-CD19.22.BBz有限的CAR T细胞扩增和持久性促使实验室对比了EF1a和MSCV的启动子,但未发现明显差异。通过体外细胞因子分泌和人源化小鼠白血病根除,来评估通过CD19.22.BBz限制性靶向CD22,导致构建了一种新型双细胞基质CD19.28z/CD22.BBz,该结构可增强对CD22的细胞因子分泌。

总之,该研究在一个CAYA B-ALL队列中证明了CD19.22.BBz的安全性和有效性,同时进一步优化了组合抗原靶向,有助于克服已明确的局限性。

 

原始出处:

Shalabi Haneen,Qin Haiying,Su Angela et al. CD19/22 CAR T cells in children and young adults with B-ALL: phase 1 results and development of a novel bicistronic CAR.[J] .Blood, 2022, 140: 451-463.

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    2022-08-12 膀胱癌
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    2022-08-12 dingxiaobo
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    2022-08-11 仁术2021

    不错学习了。

    0

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