Safe and potent anti-CD19 CAR T-cells with shRNA-IL-6 gene silencing element in patients with refractory or relapsed B-cell acute lymphoblastic leukemia

Ma, Jin-Feng1,2,3; Yan, Jia-Wei1,3; Liu, Mei-Jing1,3; Yan, Chun-Long2; Tang, Xiao-Wen1,3; Qiu, Hui-Ying1,3; Miao, Miao1,3; Han, Yue1,3; Li, Li-Min4; Kang, Li-Qing5; Xu, Nan5; Yu, Zhou5; Tan, Jing-Wen5; Zhu, Hong-Jia5; Jia, Xu5; Zhang, Zhi-Zhi1,3; Wang, Miao1,3; Dai, Hai-Ping1,3; Yu, Lei5; Xue, Sheng-Li1,3; Wu, De-Pei1,3; Gong, Wen-Jie1,3

2024-10-01

10.1002/hem3.70007

HEMASPHERE   影响因子和分区

2572-9241

Severe cytokine release syndrome (sCRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)-cell therapy. We designed a novel anti-CD19 CAR (ssCART-19) with a small hairpin RNA (shRNA) element to silence the interleukin-6 (IL-6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART-19 with common CAR T-cells (cCART-19) in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Among 87 patients, 47 received ssCART-19 and 40 received cCART-19. Grade >= 3 CRS occurred in 14.89% (7/47) of the ssCART-19 group versus 37.5% (15/40) in the cCART-19 group (p = 0.036). ICANS occurred in 4.26% (2/47) of the ssCART-19 group (all grade 1) compared to 15% (2/40) of the cCART-19 group. Patients in the ssCART-19 group showed comparable rates of treatment response (calculated with rates of complete remission and incomplete hematological recovery) were 91.49% (43/47) for ssCART-19 and 85% (34/40) for cCART-19 (p = 0.999). With a median follow-up of 21.9 months, cumulative nonrelapse mortality was 10.4% for ssCART-19 and 13.6% for cCART-19 (p = 0.33). Median overall survival was 37.17 months for ssCART-19 and 32.93 months for cCART-19 (p = 0.40). Median progression-free survival was 24.17 months for ssCART-19 and 9.33 months for cCART-19 (p = 0.23). These data support the safety and efficacy of ssCART-19 for r/r B-ALL, suggesting its potential as a promising therapy.

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英语

其他

Hematology

Hematology

WOS:001326820700001

WILEY

Web of Science

1.Soochow Univ, Affiliated Hosp 1, Jiangsu Inst Hematol, Natl Clin Res Ctr Hematol Dis, Suzhou, Peoples R China
2.Jining 1 Peoples Hosp, Dept Hematol, Jining, Peoples R China
3.Soochow Univ, Inst Blood & Marrow Transplantat, Collaborat Innovat Ctr Hematol, Suzhou, Peoples R China
4.Southern Univ Sci & Technol Hosp, Dept Hematol, Shenzhen, Peoples R China
5.Shanghai Unicar Therapy Biomed Technol Co Ltd, Res & Dev Dept, Shanghai, Peoples R China

Ma, Jin-Feng,Yan, Jia-Wei,Liu, Mei-Jing,et al. Safe and potent anti-CD19 CAR T-cells with shRNA-IL-6 gene silencing element in patients with refractory or relapsed B-cell acute lymphoblastic leukemia[J]. HEMASPHERE,2024,8(10).

Ma, Jin-Feng.,Yan, Jia-Wei.,Liu, Mei-Jing.,Yan, Chun-Long.,Tang, Xiao-Wen.,...&Gong, Wen-Jie.(2024).Safe and potent anti-CD19 CAR T-cells with shRNA-IL-6 gene silencing element in patients with refractory or relapsed B-cell acute lymphoblastic leukemia.HEMASPHERE,8(10).

Ma, Jin-Feng,et al."Safe and potent anti-CD19 CAR T-cells with shRNA-IL-6 gene silencing element in patients with refractory or relapsed B-cell acute lymphoblastic leukemia".HEMASPHERE 8.10(2024).