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苏帅, 肖毅. CAR-NK疗法在急性髓系白血病中的应用研究进展[J]. 肿瘤防治研究, 2026, 53(4): 281-288.
SU Shuai, XIAO Yi. Research Advances in Application of CAR-NK Therapy for Acute Myeloid Leukemia[J]. 2026, 53(4): 281-288.
苏帅, 肖毅. CAR-NK疗法在急性髓系白血病中的应用研究进展[J]. 肿瘤防治研究, 2026, 53(4): 281-288. DOI: 10.3971/j.issn.1000-8578.2026.25.0749.
SU Shuai, XIAO Yi. Research Advances in Application of CAR-NK Therapy for Acute Myeloid Leukemia[J]. 2026, 53(4): 281-288. DOI: 10.3971/j.issn.1000-8578.2026.25.0749.
嵌合抗原受体T细胞(CAR-T)免疫疗法在B系血液系统肿瘤中已取得突破性进展,然而在急性髓系白血病(AML)中,因缺乏高度特异的肿瘤抗原,且部分靶点在正常造血干/祖细胞上同样表达,其疗效与可控性受限,因此可能出现显著的骨髓抑制及细胞因子释放综合征(CRS)等不良反应。相较之下,CAR-NK细胞免疫疗法作为一种新兴策略,依托NK细胞的天然抗肿瘤活性,表现出较低的CRS与移植物抗宿主病(GVHD)风险,早期临床研究亦提示其具有良好的安全性与抗肿瘤活性。本文聚焦CAR-NK疗法在AML治疗中的最新进展,并对未来发展趋势与潜在突破方向加以展望。
Chimeric antigen receptor (CAR) T-cell therapy for B-cell hematologic malignancies has achieved breakthrough success; however
its efficacy for acute myeloid leukemia (AML) is constrained by the lack of highly specific tumor antigens and the expression of shared targets on normal hematopoietic stem/progenitor cells
increasing the risk of on-target myelosuppression and cytokine release syndrome (CRS). By contrast
CAR-NK cell therapy
an emerging strategy that leverages the innate antitumor activity of natural killer cells
is associated with low rates of CRS and graft-versus-host disease. Early clinical studies also indicate its favorable safety profile with preliminary antileukemic activity. This review summarizes recent advances in CAR-NK therapy for AML and discusses future directions and potential avenues for clinical translation.
Gill S, Tasian SK, Ruella M, et al . Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells[J ] . Blood, 2014, 123(15): 2343-2354.
Wei W, Yang D, Chen X, et al . Chimeric antigen receptor T-cell therapy for T-ALL and AML[J ] . Front Oncol, 2022, 12: 967754.
Liu E, Marin D, Banerjee P, et al . Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors[J ] . N Engl J Med, 2020, 382(6): 545-553.
Saadh MJ, Torabi Fard N, Hussein A, et al . Mesenchymal stem cells in the bone marrow microenvironment: a double-edged sword for AML[J ] . J Cancer Res Clin Oncol, 2025, 151(6): 193.
Tang X, Yang L, Li Z, et al . First-in-man clinical tri al of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia[J ] . Am J Cancer Res, 2018, 8(6): 1083-1089.
Huang R, Wang X, Yan H, et al . Safety and efficacy of CD33-targeted CAR-NK cell therapy for relapsed/refractory AML: preclinical evaluation and phase Ⅰ trial[J ] . Exp Hematol Oncol, 2025, 14(1): 1.
Sauter CS, Borthakur G, Mountjoy L, et al . A Phase 1 Study of NKX101, a Chimeric Antigen Receptor Natural Killer (CAR-NK) Cell Therapy, with Fludarabine and Cytarabine in Patients with Acute Myeloid Leukemia[J ] . Blood, 2023, 142(Supplement 1): 2097.
Huang R, Li X, He Y, et al . Recent advances in CAR-T cell engineering[J ] . J Hematol Oncol, 2020, 13(1): 86.
Garrison B, Deng H, Yucel G, et al . Senti-202, a Selective, Off-the-Shelf, Preclinical CAR-NK Cell Therapy with CD33 and/or FLT3 Activating CAR, Healthy Cell Protection from Endomucin (EMCN) Inhibitory CAR and Calibrated Release IL-15 for Hematologic Malignancies Including AML[J ] . Blood, 2022, 140(Supplement 1): 4531-4532.
Perriello VM, Gionfriddo I, Rossi R, et al . CD123 Is Consistently Expressed on NPM1-Mutated AML Cells[J ] . Cancers (Basel), 2021, 13(3): 496.
Testa U, Riccioni R, Militi S, et al . Elevated expression of IL-3Ralpha in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis[J ] . Blood, 2002, 100(8): 2980-2988.
Fiorenza S, Turtle CJ. CAR-T Cell Therapy for Acute Myeloid Leukemia: Preclinical Rationale, Current Clinical Progress, and Barriers to Success[J]. BioDrugs, 2021, 35(3): 281-302.
Caruso S, De Angelis B, Del Bufalo F, et al . Safe and effective off-the-shelf immunotherapy based on CAR. CD123-NK cells for the treatment of acute myeloid leukaemia[J ] . J Hematol Oncol, 2022, 15(1): 163.
Rahnama R, Kizerwetter M, Yang H, et al . Single-chain variable fragment affinity tuning can optimize anti-AML CAR-NK cell functionality[J ] . J Immunother Cancer, 2025, 13(2): e010763.
Christodoulou I, Ho WJ, Marple A, et al . Engineering CAR-NK cells to secrete IL-15 sustains their anti-AML functionality but is associated with systemic toxicities[J ] . J Immunother Cancer, 2021, 9(12): e003894.
Soleimani Samarkhazan H, Zeht abcheh S, Seraji HR, et al . Unveiling the potential of CLL-1: a promising target for AML therapy[J ] . Biomark Res, 2025, 13(1): 28.
Zhang H, Bu C, Peng Z, et al . Characteristics of anti-CLL1 based CAR-T therapy for children with relapsed or refractory acute myeloid leukemia: the multi-center efficacy and safety interim analysis[J ] . Leukemia, 2022, 36(11): 2596-2604.
Jin X, Zhang M, Sun R, et al . First-in-human phase I study of CLL-1 CAR-T cells in adults with relapsed/refractory acute myeloid leukemia[J ] . J Hematol Oncol, 2022, 15(1): 88.
Sedloev DN, Chen Q, Unglaub JM, et al . Structurally Optimized, IL-2-Armored CLL1 CAR-NK Cells Are Highly Potent Effectors Against AML without Hpsc Toxicity[J ] . Blood, 2024, 144 (Supplement 1): 3440.
Shi Y, Hao D, Qian H, et al . Natural killer cell-based cancer immunotherapy: from basics to clinical trials[J ] . Exp Hematol Oncol, 2024, 13(1): 101.
Kumar S, Mahendiran S, Nair RS, et al . A mechanistic, functional, and clinical perspective on targeting CD70 in cancer[J ] . Cancer Lett, 2024, 611: 217428.
Flieswasser T, Van Den Eynde A, Van Audenaerde J, et al . The CD70-CD27 axis in oncology: the new kids on the block[J ] . J Exp Clin Cancer Res, 2022, 41(1): 12.
Sauer T, Parikh K, Sharma S, et al . CD70-specific CAR T cells have potent activity against acute myeloid leukemia without HSC toxicity[J ] . Blood, 2021, 138(4): 318-330.
Wang L, Wang Y, He X, et al . CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells[J ] . Cell Rep Med, 2025, 6(1): 101889.
Wolf Y, Anderson AC, Kuchroo VK. TIM3 comes of age as an inhibitory receptor[J]. Nat Rev Immunol, 2020, 20(3): 173-185.
Brunner AM, Esteve J, Porkka K, et al . Phase Ⅰb study of sabatolimab (MBG453), a novel immunotherapy targeting TIM-3 antibody, in combination with decitabine or azacitidine in high- or very high-risk myelodysplastic syndromes[J ] . Am J Hematol, 2024, 99(2): E32-E36.
Klaihmon P, Samart P, Rojanasakul Y, et al . Anti-TIM3 chimeric antigen receptor-natural killer cells preferentially target primitive acute myeloid leukemia cells with minimal fratricide and exhaustion[J ] . Exp Hematol Oncol, 2024, 13(1): 67.
Klaihmon P, Luanpitpong S, Kang X, et al . Anti-TIM3 chimeric antigen receptor-natural killer cells from engineered induced pluripotent stem cells effectively target acute myeloid leukemia cells[J ] . Cancer Cell Int, 2023, 23(1): 297.
Gurney M, Stikvoort A, Nolan E, et al . CD38 knockout natural killer cells expressing an affinity optimized CD38 chimeric antigen receptor successfully target acute myeloid leukemia with reduced effector cell fratricide[J ] . Haematologica, 2022, 107(2): 437-445.
Lin Y, Xiao Z, Hu F, et al . Engineered CRO-CD7 CAR-NK cells derived from pluripotent stem cells avoid fratricide and efficiently suppress human T-cell malignancies[J ] . J Hematol Oncol, 2025, 18(1): 57.
Ran GH, Lin YQ, Tian L, et al . Natural killer cell homing and trafficking in tissues and tumors: from biology to application[J ] . Signal Transduct Target Ther, 2022, 7(1): 205.
He X, Wang L, Zeng W, et al . Regulatable C-X-C chemokine receptor type 4 in iPSC-derived NK cells improves bone marrow chemotaxis and targeting resident tumor[J ] . Trends Biotechnol, 2025, 43(7): 1668-1689.
Ladikou EE, Chevassut T, Pepper CJ, et al . Dissecting the role of the CXCL12/CXCR4 axis in acute myeloid leukaemia[J ] . Br J Haematol, 2020, 189(5): 815-825.
Liu F, Tarannum M, Zhao Y, et al . One-Step Construction of Allogeneic CAR-NK Cells Preventing Rejection and Mediating Enhanced Anti-Tumor Responses[J ] . Blood, 2024, 144(Supplement 1): 915.
Wang H, Feng S, Zhu Y, et al . The tandem CD33-CLL1 CAR-T as an approach to treat acute myeloid leukemia[J ] . Blood Transfus, 2025, 23(4): 338-347.
Xie J, Liu XF, Zhou T, et al . Overexpressing natural killer group 2 member A drives natural killer cell exhaustion in relapsed acute myeloid leukemia[J ] . Signal Transduct Target Ther, 2025, 10(1): 143.
Carter JL, Hege K, Yang J, et al . Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy[J ] . Signal Transduct Target Ther, 2020, 5(1): 288.
D'silva SZ, Singh M, Pinto AS. NK cell defects: implication in acute myeloid leukemia[J]. Front Immunol, 2023, 14: 1112059.
Yang K, Zhao Y, Sun G, et al . Clinical application and prospect of immune checkpoint inhibitors for CAR-NK cell in tumor immunotherapy[J ] . Front Immunol, 2022, 13: 1081546.
Zhu H, Blum RH, Bernareggi D, et al . Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-tumor Activity[J ] . Cell Stem Cell, 2020, 27(2): 224-237. e6.
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