Evolving strategies to overcome barriers in CAR-T cell therapy for acute myeloid leukemia.

IF 2.3 4区医学 Q2 HEMATOLOGY Expert Review of Hematology Pub Date : 2024-11-01 Epub Date: 2024-10-30 DOI:10.1080/17474086.2024.2420614

Chanukya K Colonne, Erik L Kimble, Cameron J Turtle

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Abstract

Introduction: Acute myeloid leukemia (AML) is a complex and heterogeneous disease characterized by an aggressive clinical course and limited efficacious treatment options in the relapsed/refractory (R/R) setting. Chimeric antigen receptor (CAR)-modified T (CAR-T) cell immunotherapy is an investigational treatment strategy for R/R AML that has shown some promise. However, obstacles to successful CAR-T cell immunotherapy for AML remain.

Areas covered: In analyses of clinical trials of CAR-T cell therapy for R/R AML, complete responses without measurable residual disease have been reported, but the durability of those responses remains unclear. Significant barriers to successful CAR-T cell therapy in AML include the scarcity of suitable tumor-target antigens (TTA), inherent T cell functional deficits, and the immunoinhibitory and hostile tumor microenvironment (TME). This review will focus on these barriers to successful CAR-T cell therapy in AML, and discuss scientific advancements and evolving strategies to overcome them.

Expert opinion: Achieving durable remissions in R/R AML will likely require a multifaceted approach that integrates advancements in TTA selection, enhancement of the intrinsic quality of CAR-T cells, and development of strategies to overcome inhibitory mechanisms in the AML TME.

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克服急性髓性白血病 CAR-T 细胞疗法障碍的不断发展的战略。

导言：急性髓性白血病（AML）是一种复杂的异质性疾病，临床过程凶险，复发/难治性（R/R）治疗方案疗效有限。嵌合抗原受体（CAR）修饰的T（CAR-T）细胞免疫疗法是治疗复发性/难治性急性髓细胞白血病的一种研究性治疗策略，已显示出一定的前景。然而，CAR-T细胞免疫疗法成功治疗急性髓细胞性白血病的障碍依然存在：在对CAR-T细胞疗法治疗R/R急性髓细胞性白血病的临床试验分析中，有报告称出现了无可测量残留疾病的完全应答，但这些应答的持久性仍不清楚。CAR-T细胞疗法成功治疗急性髓细胞性白血病的主要障碍包括合适的肿瘤靶抗原（TTA）稀缺、固有的T细胞功能缺陷以及免疫抑制和敌对的肿瘤微环境（TME）。这篇综述将重点探讨这些阻碍CAR-T细胞疗法在急性髓细胞性白血病中取得成功的障碍，并讨论克服这些障碍的科学进展和不断发展的策略：在R/R急性髓细胞性白血病中实现持久缓解可能需要多方面的方法，其中包括TTA选择的进步、CAR-T细胞内在质量的提高以及克服急性髓细胞性白血病TME中抑制机制的策略的开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Hematology HEMATOLOGY-

CiteScore

4.70

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Advanced molecular research techniques have transformed hematology in recent years. With improved understanding of hematologic diseases, we now have the opportunity to research and evaluate new biological therapies, new drugs and drug combinations, new treatment schedules and novel approaches including stem cell transplantation. We can also expect proteomics, molecular genetics and biomarker research to facilitate new diagnostic approaches and the identification of appropriate therapies. Further advances in our knowledge regarding the formation and function of blood cells and blood-forming tissues should ensue, and it will be a major challenge for hematologists to adopt these new paradigms and develop integrated strategies to define the best possible patient care. Expert Review of Hematology (1747-4086) puts these advances in context and explores how they will translate directly into clinical practice.