从诱导多能干细胞生成肿瘤靶向的人 T 淋巴细胞用于癌症治疗。
Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy.
机构信息
Center for Cell Engineering, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
出版信息
Nat Biotechnol. 2013 Oct;31(10):928-33. doi: 10.1038/nbt.2678. Epub 2013 Aug 11.
Abstract
Progress in adoptive T-cell therapy for cancer and infectious diseases is hampered by the lack of readily available, antigen-specific, human T lymphocytes. Pluripotent stem cells could provide an unlimited source of T lymphocytes, but the therapeutic potential of human pluripotent stem cell-derived lymphoid cells generated to date remains uncertain. Here we combine induced pluripotent stem cell (iPSC) and chimeric antigen receptor (CAR) technologies to generate human T cells targeted to CD19, an antigen expressed by malignant B cells, in tissue culture. These iPSC-derived, CAR-expressing T cells display a phenotype resembling that of innate γδ T cells. Similar to CAR-transduced, peripheral blood γδ T cells, the iPSC-derived T cells potently inhibit tumor growth in a xenograft model. This approach of generating therapeutic human T cells 'in the dish' may be useful for cancer immunotherapy and other medical applications.
摘要
嵌合抗原受体（CAR）技术与诱导多能干细胞（iPSC）技术相结合，用于在组织培养中生成靶向表达于恶性 B 细胞的抗原 CD19 的人 T 细胞。
相似文献
1
Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy.从诱导多能干细胞生成肿瘤靶向的人 T 淋巴细胞用于癌症治疗。
Nat Biotechnol. 2013 Oct;31(10):928-33. doi: 10.1038/nbt.2678. Epub 2013 Aug 11.
2
Induced Pluripotent Stem Cells (iPSCs) Provide a Potentially Unlimited T Cell Source for CAR-T Cell Development and Off-the-Shelf Products.诱导多能干细胞 (iPSCs) 为 CAR-T 细胞开发和现货产品提供了潜在的无限 T 细胞来源。
Pharm Res. 2021 Jun;38(6):931-945. doi: 10.1007/s11095-021-03067-z. Epub 2021 Jun 10.
3
Non-clinical efficacy, safety and stable clinical cell processing of induced pluripotent stem cell-derived anti-glypican-3 chimeric antigen receptor-expressing natural killer/innate lymphoid cells.诱导多能干细胞衍生的抗 GPC3 嵌合抗原受体表达的自然杀伤/固有淋巴细胞的非临床疗效、安全性和稳定的临床细胞处理。
Cancer Sci. 2020 May;111(5):1478-1490. doi: 10.1111/cas.14374. Epub 2020 Mar 31.
4
Revolutionizing Cancer Treatments through Stem Cell-Derived CAR T Cells for Immunotherapy: Opening New Horizons for the Future of Oncology.通过干细胞衍生的 CAR T 细胞进行免疫疗法彻底改变癌症治疗：为肿瘤学的未来开辟新视野。
Cells. 2024 Sep 10;13(18):1516. doi: 10.3390/cells13181516.
5
Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor T Cells: The Intersection of Stem Cells and Immunotherapy.诱导多能干细胞衍生嵌合抗原受体 T 细胞：干细胞与免疫疗法的交汇点。
Cell Reprogram. 2023 Oct;25(5):195-211. doi: 10.1089/cell.2023.0041. Epub 2023 Sep 29.
6
Induced Pluripotent Stem Cell-Derived T Cells for Cancer Immunotherapy.用于癌症免疫治疗的诱导多能干细胞衍生T细胞
Surg Oncol Clin N Am. 2019 Jul;28(3):489-504. doi: 10.1016/j.soc.2019.02.005. Epub 2019 Apr 10.
7
Modification of hematopoietic stem/progenitor cells with CD19-specific chimeric antigen receptors as a novel approach for cancer immunotherapy.用 CD19 特异性嵌合抗原受体修饰造血干细胞/祖细胞作为癌症免疫治疗的新方法。
Hum Gene Ther. 2013 Oct;24(10):824-39. doi: 10.1089/hum.2012.202.
8
Strength of CAR signaling determines T cell versus ILC differentiation from pluripotent stem cells.CAR 信号的强度决定了多能干细胞向 T 细胞与 ILC 的分化。
Cell Rep. 2023 Mar 28;42(3):112241. doi: 10.1016/j.celrep.2023.112241. Epub 2023 Mar 11.
9
Induced Pluripotent Stem Cell (iPSC)-Derived Lymphocytes for Adoptive Cell Immunotherapy: Recent Advances and Challenges.用于过继性细胞免疫治疗的诱导多能干细胞（iPSC）来源的淋巴细胞：最新进展与挑战
Curr Hematol Malig Rep. 2019 Aug;14(4):261-268. doi: 10.1007/s11899-019-00528-6.
10
3D-organoid culture supports differentiation of human CAR iPSCs into highly functional CAR T cells.3D 类器官培养支持人源性 CAR iPSCs 分化为功能强大的 CAR T 细胞。
Cell Stem Cell. 2022 Apr 7;29(4):515-527.e8. doi: 10.1016/j.stem.2022.02.009. Epub 2022 Mar 11.
引用本文的文献
1
Nanotechnology for CAR T cells and tumour-infiltrating lymphocyte therapies.用于嵌合抗原受体T细胞和肿瘤浸润淋巴细胞疗法的纳米技术。
Nat Nanotechnol. 2025 Sep 10. doi: 10.1038/s41565-025-02008-w.
2
Induced Pluripotent Stem Cell-Based Cancer Immunotherapy: Strategies and Perspectives.基于诱导多能干细胞的癌症免疫疗法：策略与展望。
Biomedicines. 2025 Aug 19;13(8):2012. doi: 10.3390/biomedicines13082012.
3
Development of iPSC-derived T cells targeting EGFR neoantigens in non-small cell lung cancer.针对非小细胞肺癌中表皮生长因子受体（EGFR）新抗原的诱导多能干细胞（iPSC）衍生T细胞的研发
Mol Ther Methods Clin Dev. 2025 Jun 18;33(3):101517. doi: 10.1016/j.omtm.2025.101517. eCollection 2025 Sep 11.
4
WNT signaling in human pluripotent stem cells promotes HDAC2-dependent epigenetic programs and development of retinoic acid-responsive mesoderm.人类多能干细胞中的WNT信号传导促进了依赖HDAC2的表观遗传程序以及视黄酸反应性中胚层的发育。
bioRxiv. 2025 Jun 8:2025.06.06.657928. doi: 10.1101/2025.06.06.657928.
5
Regenerative Immunotherapy for Cancer: Transcription Factor Reprogramming of Tumor-Specific T Cells.癌症的再生免疫疗法：肿瘤特异性T细胞的转录因子重编程
Cancers (Basel). 2025 Jul 2;17(13):2225. doi: 10.3390/cancers17132225.
6
Engineering the next generation of allogeneic CAR cells: iPSCs as a scalable and editable platform.构建下一代同种异体嵌合抗原受体（CAR）细胞：诱导多能干细胞（iPSC）作为一个可扩展且可编辑的平台
Stem Cell Reports. 2025 Jul 8;20(7):102515. doi: 10.1016/j.stemcr.2025.102515. Epub 2025 Jun 5.
7
From induced pluripotent stem cell (iPSC) to universal immune cells: literature review of advances in a new generation of tumor therapies.从诱导多能干细胞（iPSC）到通用免疫细胞：新一代肿瘤治疗进展的文献综述
Transl Cancer Res. 2025 Apr 30;14(4):2495-2507. doi: 10.21037/tcr-24-1087. Epub 2025 Apr 15.
8
Regulatory T cell therapy for Graft-versus-Host Disease.移植物抗宿主病的调节性T细胞疗法
Bone Marrow Transplant. 2025 Apr 16. doi: 10.1038/s41409-025-02553-x.
9
Engineering innate immune cells for cancer immunotherapy.通过工程改造天然免疫细胞进行癌症免疫治疗。
Nat Biotechnol. 2025 Apr;43(4):516-533. doi: 10.1038/s41587-025-02629-5. Epub 2025 Apr 14.
10
Bioengineered therapeutic systems for improving antitumor immunity.用于增强抗肿瘤免疫力的生物工程治疗系统。
Natl Sci Rev. 2024 Nov 12;12(1):nwae404. doi: 10.1093/nsr/nwae404. eCollection 2025 Jan.
本文引用的文献
1
HLA engineering of human pluripotent stem cells.人类多能干细胞的 HLA 工程。
Mol Ther. 2013 Jun;21(6):1232-41. doi: 10.1038/mt.2013.59. Epub 2013 Apr 30.
2
The basic principles of chimeric antigen receptor design.嵌合抗原受体设计的基本原则。
Cancer Discov. 2013 Apr;3(4):388-98. doi: 10.1158/2159-8290.CD-12-0548. Epub 2013 Apr 2.
3
CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia.CD19 靶向 T 细胞可迅速诱导化疗耐药的成人急性淋巴细胞白血病患者达到分子缓解。
Sci Transl Med. 2013 Mar 20;5(177):177ra38. doi: 10.1126/scitranslmed.3005930.
4
Deciphering the hierarchy of angiohematopoietic progenitors from human pluripotent stem cells.从人类多能干细胞中解析脉管造血祖细胞的层次结构。
Cell Cycle. 2013 Mar 1;12(5):720-7. doi: 10.4161/cc.23823. Epub 2013 Feb 6.
5
Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation.通过重编程为多能性和再分化产生年轻化的抗原特异性 T 细胞。
Cell Stem Cell. 2013 Jan 3;12(1):114-26. doi: 10.1016/j.stem.2012.11.002.
6
Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8(+) T cells.从成熟 CD8(+) T 细胞衍生的 iPSCs 中再生人类肿瘤抗原特异性 T 细胞。
Cell Stem Cell. 2013 Jan 3;12(1):31-6. doi: 10.1016/j.stem.2012.12.006.
7
What lessons can be learned from γδ T cell-based cancer immunotherapy trials?从基于 γδ T 细胞的癌症免疫疗法试验中可以吸取哪些经验教训？
Cell Mol Immunol. 2013 Jan;10(1):35-41. doi: 10.1038/cmi.2012.39. Epub 2012 Dec 17.
8
T lymphocyte potential marks the emergence of definitive hematopoietic progenitors in human pluripotent stem cell differentiation cultures.T 淋巴细胞潜能标志着人类多能干细胞分化培养中明确造血祖细胞的出现。
Cell Rep. 2012 Dec 27;2(6):1722-35. doi: 10.1016/j.celrep.2012.11.003. Epub 2012 Dec 7.
9
Generating an iPSC bank for HLA-matched tissue transplantation based on known donor and recipient HLA types.基于已知供者和受者 HLA 类型，生成与 HLA 匹配的组织移植用 iPSC 库。
Cell Stem Cell. 2012 Aug 3;11(2):147-52. doi: 10.1016/j.stem.2012.07.014.
10
Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer.锌指核酸酶和慢病毒基因转移编辑 T 细胞对白血病的特异性。
Nat Med. 2012 May;18(5):807-815. doi: 10.1038/nm.2700.
Zotero 插件