决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.
选择更有效、更安全的 CAR T 细胞治疗对于改善急性白血病的总生存期至关重要。
背景:复发/难治性 B 细胞急性淋巴细胞白血病(r/r B-ALL)是预后困难的儿童癌症。CAR-T 被视为先进治疗,但由于复发率高和不良事件,疗效仍有争议。本研究评估 CAR-T 治疗 r/r B-ALL 的疗效和安全性。 方法:在四个数据库中检索文献。疗效指标包括微小残留病阴性完全缓解(MRD-CR)率和复发率(RR);安全性指标包括细胞因子释放综合征(CRS)及免疫效应细胞相关神经毒性综合征(ICANS)。 结果:与抗 CD19 相比,抗 CD22 的 MRD-CR 事件率最高、RR 最低,疗效更优。CAR-T 联合单倍体干细胞移植可改善 RR。安全性方面,抗 CD19/22 双特异性 CAR-T 的 CRS 率最低,抗 CD22 的 ICANS 最少。共刺激受体分析显示,在抗 CD19 CAR-T 中加入 CD28 可更有效减少复发,且安全性良好。 结论:选择疗效更优且更安全的 CAR-T 治疗对改善急性白血病总生存至关重要。除前景良好的抗 CD22 CAR-T 外,探索共刺激结构域和新的 CD 靶点也可能提高 r/r B-ALL 治疗效果。
BACKGROUND: Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL. METHODS: The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). RESULTS: Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28 to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles. CONCLUSION: Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.
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