Acute myeloid leukemia (AML) is a heterogeneous and aggressive hematologic malignancy with poor prognosis despite multiple available therapies. While chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of B-cell malignancies, its application in AML has been limited by early relapses and severe toxicities. Unlike B-cell antigens, most AML-associated surface antigens are also expressed on healthy hematopoietic stem and progenitor cells, creating significant risks of on-target/off-tumor toxicity and prolonged myeloablation. To address the scarcity of AML-specific targets, several innovative CAR strategies have been developed to enhance precision, safety, and efficacy. Logic-gated CARs improve selectivity through dual-antigen recognition or conditional activation. Drug-inducible and transient expression systems, as well as pharmacologic or suicide switches, enable controlled modulation or elimination of CAR cells to reduce toxicity. Adapter CAR platforms allow real-time, flexible targeting, while engineered modulation of gene expression or cytokine secretion enhances persistence and antitumor activity. Finally, alternative immune cells, including natural killer (NK) cells and macrophages, provide versatile platforms that may overcome limitations of conventional T-cell therapies, such as fratricide or challenges in allogeneic use. This review provides a comprehensive overview of these emerging CAR approaches, highlighting their advantages, limitations, and potential to expand immunotherapeutic strategies for AML.
急性髓系白血病（AML）是一种异质性强、侵袭性高的血液系统恶性肿瘤，尽管现有多种治疗手段，其预后仍然较差。嵌合抗原受体（CAR）T细胞疗法虽已彻底改变B细胞恶性肿瘤的治疗格局，但在AML中的应用因早期复发和严重毒性反应而受限。与B细胞抗原不同，大多数AML相关表面抗原同样在健康造血干细胞和祖细胞上表达，这导致显著的靶向/脱肿瘤毒性风险及长期骨髓抑制问题。为应对AML特异性靶点稀缺的挑战，多种创新性CAR策略已被开发，以提升治疗的精准性、安全性和有效性。逻辑门控CAR通过双抗原识别或条件性激活机制提高选择性；药物诱导型及瞬时表达系统，以及药理学或自杀开关设计，实现了对CAR细胞的可控调节或清除以降低毒性；适配器CAR平台支持实时灵活的靶向调控；而基因表达或细胞因子分泌的工程化改造则增强了CAR细胞的持久性与抗肿瘤活性。此外，自然杀伤（NK）细胞和巨噬细胞等替代性免疫细胞为克服传统T细胞疗法局限性（如自相残杀或同种异体应用难题）提供了多功能平台。本文系统综述了这些新兴CAR策略，重点探讨其优势、局限性以及在拓展AML免疫治疗策略方面的潜力。
The Rise of Fine-Tuned CAR-Based Therapies Against Acute Myeloid Leukemia
肿瘤(癌症)患者之家