急性髓系白血病CAR-T细胞治疗的免疫屏障和工程策略
Immunological barriers and engineering strategies for CAR-T cell therapy in acute myeloid leukemia.
摘要(中文译文)
急性髓系白血病（AML）仍然是一种难以治疗的疾病，尤其是在复发或难治性患者中。尽管嵌合抗原受体T细胞（CAR-T）疗法已经改变了多种B细胞恶性肿瘤的治疗格局，但其在AML中的临床疗效却明显更为有限。这种有限的疗效不仅反映了CAR设计方面的挑战，也反映了AML固有的复杂生物学和免疫学屏障。靶点特异性不足、显著的白血病异质性以及免疫抑制性骨髓微环境共同损害了CAR-T细胞的识别、持久性和效应功能，从而限制了其治疗疗效和安全性。在本综述中，我们讨论这些主要屏障，并总结为应对这些屏障而开发的新兴工程化策略，包括提高靶向精确性、增强CAR-T细胞功能适应性以及重塑抑制性免疫微环境的方法。总之，这些见解可能有助于阐明有效CAR-T疗法在AML中的关键障碍，并为未来优化该疗法的策略提供参考。
Abstract
Acute myeloid leukemia (AML) remains a difficult disease to treat, especially in patients with relapsed or refractory disease. While chimeric antigen receptor T cell (CAR-T) therapy has transformed the treatment landscape of several B-cell malignancies, its clinical efficacy in AML has been substantially more limited. This limited efficacy reflects not only challenges in CAR design, but also the complex biological and immunological barriers inherent to AML. Insufficient target specificity, pronounced leukemic heterogeneity, and an immunosuppressive bone marrow microenvironment collectively impair CAR-T cell recognition, persistence, and effector function, thereby restricting both therapeutic efficacy and safety. In this review, we discuss these major barriers and summarize emerging engineering strategies developed to address them, including approaches to improve targeting precision, reinforce CAR-T cell functional fitness, and remodel the suppressive immune niche. Together, these insights may help clarify the key barriers to effective CAR-T therapy in AML and inform future strategies for its optimization.
如何引用
AMA
Ya Wang, Tiantian Yu, Ming Wang, Li Yu. Immunological barriers and engineering strategies for CAR-T cell therapy in acute myeloid leukemia.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1837609.
APA
Ya Wang, Tiantian Yu, Ming Wang, Li Yu (2026). Immunological barriers and engineering strategies for CAR-T cell therapy in acute myeloid leukemia.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1837609
GB/T 7714
Ya Wang, Tiantian Yu, Ming Wang, Li Yu. Immunological barriers and engineering strategies for CAR-T cell therapy in acute myeloid leukemia.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1837609.
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