CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
IL-15 过表达促进临床前急性髓系白血病模型中 CD64 CAR-T 细胞的记忆程序与抗肿瘤活性
英文原题：IL-15 overexpression promotes memory program and anti-tumor activity of CD64 CAR T cells in a preclinical AML model.
查看英文原题
IL-15 overexpression promotes memory program and anti-tumor activity of CD64 CAR T cells in a preclinical AML model.
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中文摘要
复发/难治性急性髓系白血病（r/r AML）患者预后仍然较差，原因之一是缺乏新型疗法。我们此前证明，靶向CD64的嵌合抗原受体（CAR）T细胞具有治疗AML的潜力，且对造血干细胞/祖细胞的毒性较小；但其在AML小鼠模型中的疗效有限。白细胞介素-15（IL-15）可促进T细胞存活和增殖，已显示能增强CAR-T 细胞活性。本研究将IL-15过表达工程化导入CD64 CAR-T 细胞并评估其功能。经IL-15增强的CAR-T 细胞对AML细胞的细胞毒活性提高，体外扩增和持久性增强，且更倾向于形成记忆表型，同时耗竭和凋亡减少。在小鼠模型中，IL-15增强的CAR-T 细胞扩增显著、延长小鼠生存，且未见明显毒性。这些发现提示，经IL-15增强的CD64 CAR-T 细胞可能是治疗r/r AML的一种有前景策略。
展开英文摘要原文
The prognosis of relapsed or refractory acute myeloid leukemia (r/r AML) patients remains poor due to lack of novel therapies.
We previous demonstrated that chimeric antigen receptor (CAR) T cells targeting CD64 have the potential to treat AML with minimal toxicity to hematopoietic stem/progenitor cells.
However, the efficacy was limited in AML mouse models. Interleukin-15 (IL-15), a cytokine that promotes T cell survival and proliferation, has been shown to enhance CAR T cell activity.
Here, we engineer CD64 CAR T cells with overexpression of IL-15 and evaluate the function. IL-15-armed CAR T cells exhibit enhanced cytolytic activity against AML cells, improve expansion and persistence in vitro, and favor a memory phenotype while reducing exhaustion and apoptosis. In mouse model, IL-15-armed CAR T cells show robust expansion, prolong mouse survival, and no obvious toxicity.
These findings suggest that IL-15-armed CD64 CAR T cells may be a promising strategy for r/r AML.
论文信息
- 作者
- Shan L、Li C、Li T、Wang C、Cui H、Pang A、Feng X
- 第一作者单位
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.China
- 通讯作者单位
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. xfeng1979@hotmail.com.China
- 期刊
- Communications biology2026 Jan 15
- 原文标识
- PubMed 41540104 · DOI 10.1038/s42003-026-09528-8
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