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:Adult acute lymphoblastic leukemia: incorporation of recent advances into current treatment strategies.
由于治疗进展以及疾病监测和预后评估的改善,B 细胞急性淋巴细胞白血病(ALL)的结局随时间推移有所改善。
随着治疗手段进步、疾病监测和预后评估改善,B细胞急性淋巴细胞白血病(ALL)的治疗结局持续提高。BCR::ABL1酪氨酸激酶抑制剂(TKI)是首批显著改变费城染色体阳性(Ph+)ALL治疗历程和结局的靶向疗法。同样,靶向CD19/20/22的抗体及工程化嵌合抗原受体(CAR)T细胞免疫疗法,也彻底改变了B细胞ALL的治疗格局。将T细胞接合双特异性抗体(BiTE)blinatumomab纳入方案后,新诊断Ph阴性和Ph+ ALL患者的生存获益显著。抗CD22抗体药物偶联物(ADC)inotuzumab ozogamicin也已安全整合至年轻及老年患者的一线治疗方案。CAR T细胞疗法可使复发/难治性(R/R)ALL患者获得持久缓解,尤其是在疾病负荷较低时。目前正在探索将CAR T细胞疗法作为前线巩固治疗,以期减少对异基因干细胞移植(alloSCT)的需求。未来研究将聚焦优化治疗,通过免疫疗法替代化疗,以降低毒性、减少alloSCT需求并缩短治疗强度和疗程,同时改善长期结局。
Outcomes in B-cell acute lymphoblastic leukemia (ALL) have improved over time due to therapeutic advances, and improved disease monitoring and prognostication. The BCR::ABL1 tyrosine kinase inhibitors (TKIs) were the first targeted therapies to significantly impact the therapeutic trajectory and outcomes of Philadelphia chromosome-positive (Ph-positive) ALL. Similarly, antibodies targeting CD19/20/22 and engineered chimeric antigen receptor (CAR) T-cell immunotherapies have drastically changed the therapeutic landscape and outcomes of B-cell ALL. Incorporation of the bispecific T-cell engager (BiTE) blinatumomab has demonstrated a significant survival advantage in patients with both newly diagnosed Philadelphia chromosome-negative (Ph-negative) and Ph-positive ALL. Inotuzumab ozogamicin, the anti-CD22 antibody drug conjugate (ADC), has also been safely integrated into the frontline treatment backbones in both younger and older patients. CAR T-cell therapy has resulted in durable remissions in relapsed/refractory (R/R) ALL, especially with lower disease burden. CAR T-cell therapy consolidation in the frontline setting is being pursued with the goal of reducing the need for allogeneic stem cell transplantation (alloSCT). Future research is focusing on treatment optimization through replacement of chemotherapy with immunotherapies with the goal of reducing toxicities, minimizing the need for alloSCT, and shortening the intensity and duration of therapy while improving long-term outcomes.
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