Treatment with Humanized Selective CD19CAR-T Cells Shows Efficacy in Highly Treated B-ALL Patients Who Have Relapsed after Receiving Murine-Based CD19CAR-T Therapies

人源化选择性 CD19CAR-T 细胞治疗对接受鼠源 CD19CAR-T 疗法后复发的 B-ALL 患者有疗效

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作者:Yu Zhao #, Zhongfeng Liu #, Xuan Wang #, Huantong Wu, Jianping Zhang, Junfang Yang, Fayou Zhang, Lining Liu, Jiafu Long, Peihua Lu, Zhiguo Chen

Conclusions

hsCD19 CAR-T treatment shows efficacy in highly treated B-ALL patients who have relapsed after receiving CD19 mCAR-T therapies.

Purpose

CD19 chimeric antigen receptor (CAR)-T therapy has shown impactful

Results

hsCAR possessed around 6-fold higher affinity to CD19 versus murine CAR (mCAR). Incubation with selective domain-specific mAbs (SmAb) selectively expanded CAR-transduced T cells, and led to a higher proportion of central memory T cells in the final products. SmAb-stimulated CD19 hsCAR-T cells exhibited superior antitumor cytotoxic functions in vitro and in vivo. Autologous (n = 2) and allogeneic donor (n = 3, with hematopoietic stem cell transplantation) hsCAR-T cells were infused into 5 patients who had relapsed after receiving mCAR-T treatments. Two patients received mCAR-T treatments twice previously but the second treatments were ineffective. In contrast, subsequent hsCAR-T treatments proved effective in all 5 patients and achieved complete molecular remission in four, including one with extramedullary disease with central nervous system involvement. Conclusions: hsCD19 CAR-T treatment shows efficacy in highly treated B-ALL patients who have relapsed after receiving CD19 mCAR-T therapies.

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