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:Beyond Cellular Therapies: The Expanding Role of Antibody-Driven Immunotherapy in Pediatric Acute Lymphoblastic Leukemia.
儿童ALL下一轮一线试验将纳入更多免疫治疗,并减少化疗。后续试验将采用更多同步化疗免疫治疗模块,同时精准检测和风险适应性治疗将继续发展。这些进展反映了儿童ALL治疗策略向更精准、毒性更低方向的范式转变。
将新型抗体介导的靶向治疗整合到复发/难治性(R/R)和一线儿童急性淋巴细胞白血病(ALL)治疗方案中,已为该领域带来了关键性进展。当前的研究工作聚焦于优化靶向治疗,通过减少化疗来提高精准度和疗效,同时将毒性降至最低。一个显著例子是加入 blinatumomab,其疗效优于传统化疗,在一项中期分析中无病生存率提高了 8%,达到 96%。Inotuzumab ozogamicin(InO)也显示出前景,在儿童 R/R B 细胞 ALL(B-ALL)试验中达到近 70% 的完全缓解率。此外,daratumumab 用于 T 细胞 ALL(T-ALL)以及CAR-T 细胞疗法,特别是 CD19 靶向(B-ALL)和 CD7 靶向(T-ALL)策略,正在积极研究中。概述:本综述将概述 B-ALL 和 T-ALL 中靶向抗体介导的免疫治疗,重点介绍其在儿童中的应用、支持数据及未来前景。
BACKGROUND: The integration of novel antibody-mediated targeted therapies into both relapsed/refractory (R/R) and frontline pediatric acute lymphoblastic leukemia (ALL) treatment protocols has led to critical advancements in the field. Current research efforts focus on optimizing targeted therapies to enhance precision and efficacy while minimizing toxicity by reducing chemotherapy. A notable example is the addition of blinatumomab, demonstrating superiority over conventional chemotherapy, with an 8% increase in disease-free survival at an interim analysis, reaching 96%. Inotuzumab ozogamicin (InO) has also shown promise, achieving nearly a 70% complete response rate in pediatric R/R B-cell ALL (B-ALL) trials. Additionally, daratumumab in T-cell ALL (T-ALL) and chimeric antigen receptor T-cell therapies, particularly CD19-directed (B-ALL) and CD7-directed (T-ALL) strategies, are under active investigation. SUMMARY: This review will provide an overview of targeted antibody-mediated immunotherapies in both B-ALL and T-ALL, with a focus on their pediatric applications, supporting data, and future prospects. KEY MESSAGES: The next cycle of frontline trials in pediatric ALL will incorporate more immunotherapy with reduction of chemotherapy. Subsequent trials will utilize more concurrent chemoimmunotherapy blocks as precision testing and risk-adapted therapy will continue to develop. These advancements reflect a paradigm shift toward more precise, less toxic treatment strategies in pediatric ALL.
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