CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Therapeutic Strategies for Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia in Adult Patients: Optimizing the Use of Monoclonal Antibodies.
Therapeutic Strategies for Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia in Adult Patients: Optimizing the Use of Monoclonal Antibodies.
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复发/难治性急性淋巴细胞白血病(RR ALL)的治疗格局随着blinatumomab和inotuzumab ozogamicin等单克隆抗体的引入而发生了显著演变。这些药物已展现出显著疗效,可实现高缓解率和微小残留病(MRD)阴性。
然而,单克隆抗体与标准化疗或CAR-T 细胞疗法等其他方式的最佳选择、排序和整合仍是活跃的研究领域。由于缺乏直接比较研究,人们依赖于间接分析,而这些分析在inotuzumab与blinatumomab的相对获益方面提供了相互矛盾的结果。虽然inotuzumab因其减瘤能力在高疾病负荷情况下更受青睐,但blinatumomab通过利用保留的T细胞功能,在低疾病负荷情况下表现出更优的性能。序贯和联合方案,例如以inotuzumab诱导后接blinatumomab巩固,可能优化结局,特别是对于随后接受异基因干细胞移植(alloSCT)的患者。inotuzumab与alloSCT之间的间隔对于降低肝静脉闭塞病(VOD)风险至关重要。尽管取得了这些进展,具有高风险遗传病变(如TP53突变)的患者的预后仍然较差,这凸显了对创新治疗策略的需求。随着单克隆抗体日益进入一线治疗,其在复发场景中的作用必须重新定义。未来研究应侧重于揭示耐药的分子基础并完善治疗范式,以改善RR ALL患者的生存和生活质量。
The treatment landscape for relapsed or refractory acute lymphoblastic leukemia (RR ALL) has evolved significantly with the introduction of monoclonal antibodies such as blinatumomab and inotuzumab ozogamicin. These agents have demonstrated remarkable efficacy, achieving high response rates and minimal residual disease (MRD) negativity.
However, the optimal selection, sequencing, and integration of monoclonal antibodies and other modalities like standard chemotherapy or chimeric antigen receptor T-cell therapy remain areas of active investigation. The absence of direct comparative studies has led to reliance on indirect analyses, which provide conflicting results regarding the relative benefits of inotuzumab and blinatumomab. While inotuzumab is preferred in high-disease-burden settings due to its cytoreductive capabilities, blinatumomab shows superior performance in low-disease-burden settings by leveraging preserved T-cell function.
Sequential and combination approaches, such as induction with inotuzumab followed by blinatumomab consolidation, may optimize outcomes, particularly for patients undergoing subsequent allogeneic stem cell transplantation (alloSCT). The interval between inotuzumab and alloSCT is critical to mitigate the risk of veno-occlusive disease (VOD).
Despite these advances, the prognosis for patients with high-risk genetic lesions, such as TP53 mutations, remains poor, underscoring the need for innovative therapeutic strategies. As monoclonal antibodies increasingly move into frontline therapy, their role in relapse settings must be redefined. Future research should focus on unraveling the molecular underpinnings of resistance and refining treatment paradigms to improve survival and quality of life for patients with RR ALL.
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