Wu Huichao, Shafiei Fatemeh Sadat, Taghinejad Zahra, Maleknia Mohsen, Noormohamadi Hanieh, Raoufi Atieh, Nouri Sina, Servatian Nazli, Soleimani Samarkhazan Hamed
Dept Emergency, First Peoples Hosp Jiashan, Jiashan, 314100, Zhejiang, People's Republic of China.
Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran.
J Transl Med. 2025 Oct 23;23(1):1163. doi: 10.1186/s12967-025-07151-5.
Acute myeloid leukemia (AML), characterized by aggressive relapse and dismal survival, remains a formidable challenge despite conventional therapies. Chimeric antigen receptor (CAR)-engineered T and natural killer (NK) cells have emerged as groundbreaking immunotherapies, offering targeted eradication of leukemic stem cells (LSCs) and resistant blasts. CAR-T cells, leveraging antigens like CD123 and CD33, demonstrate early clinical success, with complete remission rates up to 66% in refractory/relapsed (R/R) AML. CAR-NK cells complement this approach through inherent tumor surveillance, reduced toxicity, and "off-the-shelf" feasibility. However, barriers such as antigen escape, heterogeneous immunosuppressive microenvironments (including intratumoral microbiota variations), and on-target/off-tumor toxicity persist, limiting durable responses. Innovations in dual-targeting CARs, cytokine-armored constructs, and CRISPR-edited universal cells aim to overcome these hurdles. Emerging strategies integrating checkpoint inhibitors, metabolic modulators, and AI-driven antigen selection promise to enhance efficacy and safety. This review synthesizes the evolving landscape of CAR-T/NK therapies, critically analyzing preclinical breakthroughs, clinical trial outcomes, and persisting challenges. By addressing manufacturing scalability, cost barriers, and long-term safety, cellular immunotherapy holds transformative potential to redefine AML management. As the field advances, interdisciplinary collaboration and biomarker-guided personalization will be pivotal in translating laboratory innovations into life-saving therapies for AML patients.
急性髓系白血病（AML）具有侵袭性复发和生存率低的特点，尽管采用了传统疗法，但仍然是一项艰巨的挑战。嵌合抗原受体（CAR）工程改造的T细胞和自然杀伤（NK）细胞已成为开创性的免疫疗法，可靶向清除白血病干细胞（LSC）和耐药性母细胞。CAR-T细胞利用CD123和CD33等抗原，早期临床取得成功，难治性/复发性（R/R）AML的完全缓解率高达66%。CAR-NK细胞通过固有的肿瘤监测、降低的毒性和“现成可用”的可行性来补充这种方法。然而，抗原逃逸、异质性免疫抑制微环境（包括肿瘤内微生物群变化）和靶向肿瘤外毒性等障碍仍然存在，限制了持久反应。双靶点CAR、细胞因子强化构建体和CRISPR编辑的通用细胞方面的创新旨在克服这些障碍。整合检查点抑制剂、代谢调节剂和人工智能驱动的抗原选择的新兴策略有望提高疗效和安全性。本综述综合了CAR-T/NK疗法不断变化的格局，批判性地分析了临床前突破、临床试验结果和持续存在的挑战。通过解决生产可扩展性、成本障碍和长期安全性问题，细胞免疫疗法具有重新定义AML治疗的变革潜力。随着该领域的发展，跨学科合作和生物标志物引导的个性化将对将实验室创新转化为AML患者的救命疗法至关重要。
