严重细胞因子释放综合征 (sCRS) 和免疫效应细胞相关神经毒性综合征 (ICANS) 限制了嵌合抗原受体 T (CAR T) 细胞疗法的广泛使用。我们设计了一种新型抗 CD19 CAR (ssCART-19)，其具有小发夹 RNA (shRNA) 元件来沉默白细胞介素 6 (IL-6) 基因，假设它可以通过减轻单核细胞活化和促炎细胞因子释放来减少 sCRS 和 ICANS 。在对两项临床试验的事后分析中，我们将 ssCART-19 与普通 CAR T 细胞 (cCART-19) 在复发/难治性 B 细胞急性淋巴细胞白血病 (r/r B-ALL) 中进行比较。在 87 名患者中，47 名患者接受了 ssCART-19，40 名患者接受了 cCART-19。 ssCART-19 组中 14.89% (7/47) 发生 3 级以上 CRS，而 cCART-19 组中发生率为 37.5% (15/40) (p = 0.036)。 ssCART-19 组（均为 1 级）的 ICANS 发生率为 4.26% (2/47)，而 cCART-19 组的发生率为 15% (2/40)。 ssCART-19 组患者的治疗反应率（以完全缓解率和不完全血液学恢复率计算）相当，ssCART-19 为 91.49% (43/47)，cCART-19 为 85% (34/40)。 p = 0.999）。中位随访时间为 21.9 个月，ssCART-19 的累积非复发死亡率为 10.4%，cCART-19 的累积非复发死亡率为 13.6%（p = 0.33）。 ssCART-19 的中位总生存期为 37.17 个月，cCART-19 的中位总生存期为 32.93 个月 (p = 0.40)。 ssCART-19 的中位无进展生存期为 24.17 个月，cCART-19 的中位无进展生存期为 9.33 个月（p = 0.23）。这些数据支持 ssCART-19 对于 r/r B-ALL 的安全性和有效性，表明其作为一种有前途的疗法的潜力。© 2024 作者。约翰·威利 (John Wiley) 出版的 HemaSphere

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.© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.