嵌合抗原受体 T 细胞的作用机制及功能的最新进展和发现。
Recent advances and discoveries in the mechanisms and functions of CAR T cells.
机构信息
Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, MA, USA.
Immunology Program, Harvard Medical School, Boston, MA, USA.
出版信息
Nat Rev Cancer. 2021 Mar;21(3):145-161. doi: 10.1038/s41568-020-00323-z. Epub 2021 Jan 22.
Abstract
This Review discusses the major advances and changes made over the past 3 years to our understanding of chimeric antigen receptor (CAR) T cell efficacy and safety. Recently, the field has gained insight into how various molecular modules of the CAR influence signalling and function. We report on mechanisms of toxicity and resistance as well as novel engineering and pharmaceutical interventions to overcome these challenges. Looking forward, we discuss new targets and indications for CAR T cell therapy expected to reach the clinic in the next 1-2 years. We also consider some new studies that have implications for the future of CAR T cell therapies, including changes to manufacturing, allogeneic products and drug-regulatable CAR T cells.
摘要
这篇综述讨论了过去 3 年来，我们对嵌合抗原受体 (CAR) T 细胞疗效和安全性的理解所取得的主要进展和变化。最近，该领域深入了解了 CAR 的各种分子模块如何影响信号转导和功能。我们报告了毒性和耐药性机制，以及新的工程和药物干预措施，以克服这些挑战。展望未来，我们讨论了预计在未来 1-2 年内进入临床的 CAR T 细胞治疗的新靶点和适应证。我们还考虑了一些对 CAR T 细胞治疗的未来具有影响的新研究，包括对制造、同种异体产品和可调控 CAR T 细胞的改变。
相似文献
1
Recent advances and discoveries in the mechanisms and functions of CAR T cells.嵌合抗原受体 T 细胞的作用机制及功能的最新进展和发现。
Nat Rev Cancer. 2021 Mar;21(3):145-161. doi: 10.1038/s41568-020-00323-z. Epub 2021 Jan 22.
2
The making and function of CAR cells.嵌合抗原受体（CAR）细胞的制备和功能。
Immunol Lett. 2019 Aug;212:53-69. doi: 10.1016/j.imlet.2019.06.002. Epub 2019 Jun 7.
3
Chimeric antigen receptor T-cell therapy for the treatment of aggressive B-cell non-Hodgkin lymphomas: efficacy, toxicity, and comparative chimeric antigen receptor products.嵌合抗原受体 T 细胞疗法治疗侵袭性 B 细胞非霍奇金淋巴瘤：疗效、毒性和比较嵌合抗原受体产品。
Expert Opin Biol Ther. 2019 Nov;19(11):1157-1164. doi: 10.1080/14712598.2019.1644316. Epub 2019 Jul 25.
4
Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.同种异体嵌合抗原受体 T 细胞靶向 BCMA 治疗多发性骨髓瘤的临床前评估。
Mol Ther. 2019 Jun 5;27(6):1126-1138. doi: 10.1016/j.ymthe.2019.04.001. Epub 2019 Apr 8.
5
Strategies to Circumvent the Side-Effects of Immunotherapy Using Allogeneic CAR-T Cells and Boost Its Efficacy: Results of Recent Clinical Trials.使用同种异体 CAR-T 细胞规避免疫疗法副作用并提高疗效的策略：近期临床试验结果。
Front Immunol. 2021 Dec 15;12:780145. doi: 10.3389/fimmu.2021.780145. eCollection 2021.
6
CAR-NK Cells: From Natural Basis to Design for Kill.嵌合抗原受体自然杀伤细胞：从天然基础到杀伤设计。
Front Immunol. 2021 Dec 14;12:707542. doi: 10.3389/fimmu.2021.707542. eCollection 2021.
7
Neurological Complications of CAR T Cell Therapy.嵌合抗原受体 T 细胞疗法的神经系统并发症。
Curr Oncol Rep. 2020 Jul 1;22(8):83. doi: 10.1007/s11912-020-00935-6.
8
Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia.嵌合抗原受体 T 细胞疗法治疗急性淋巴细胞白血病。
Curr Treat Options Oncol. 2020 Feb 5;21(2):16. doi: 10.1007/s11864-020-0706-6.
9
Current progress in chimeric antigen receptor T cell therapy for glioblastoma multiforme.嵌合抗原受体 T 细胞疗法治疗多形性胶质母细胞瘤的研究进展。
Cancer Med. 2021 Aug;10(15):5019-5030. doi: 10.1002/cam4.4064. Epub 2021 Jun 19.
10
Chimeric antigen receptor (CAR)-T-cell therapy in non-small-cell lung cancer (NSCLC): current status and future perspectives.嵌合抗原受体 (CAR)-T 细胞疗法在非小细胞肺癌 (NSCLC) 中的应用：现状与未来展望。
Cancer Immunol Immunother. 2021 Mar;70(3):619-631. doi: 10.1007/s00262-020-02735-0. Epub 2020 Oct 6.
引用本文的文献
1
Engineering strategies of sequential drug delivery systems for combination tumor immunotherapy.用于联合肿瘤免疫治疗的序贯给药系统的工程策略。
Acta Pharm Sin B. 2025 Aug;15(8):3951-3977. doi: 10.1016/j.apsb.2025.05.039. Epub 2025 Jun 6.
2
Blades and barriers: Oral vaccines for conquering cancers and warding off infectious diseases.利刃与屏障：用于攻克癌症和抵御传染病的口服疫苗
Acta Pharm Sin B. 2025 Aug;15(8):3925-3950. doi: 10.1016/j.apsb.2025.05.038. Epub 2025 Jun 3.
3
Inhibitory leukocyte immunoglobulin-like receptors, subfamily B (LILRBs) in human diseases: structure, roles, mechanisms, and clinical applications.人类疾病中的抑制性白细胞免疫球蛋白样受体B亚家族（LILRBs）：结构、作用、机制及临床应用
Theranostics. 2025 Jul 25;15(16):8222-8258. doi: 10.7150/thno.116951. eCollection 2025.
4
Unveiling the influence of CAR-negative T-cells: enhancing efficacy and ensuring safety in CAR-T therapies.揭示CAR阴性T细胞的影响：提高CAR-T疗法的疗效并确保安全性。
J Transl Med. 2025 Aug 19;23(1):942. doi: 10.1186/s12967-025-06899-0.
5
production of CAR T cell: Opportunities and challenges.嵌合抗原受体T细胞的生产：机遇与挑战。
Genes Dis. 2025 Mar 25;12(6):101612. doi: 10.1016/j.gendis.2025.101612. eCollection 2025 Nov.
6
SCAN-ACT: adoptive T cell therapy target discovery through single-cell transcriptomics.SCAN-ACT：通过单细胞转录组学发现过继性T细胞疗法的靶点
Genome Med. 2025 Aug 14;17(1):89. doi: 10.1186/s13073-025-01514-9.
7
Nanotechnology for immuno-oncology.免疫肿瘤学的纳米技术
Nat Cancer. 2025 Aug 7. doi: 10.1038/s43018-025-01025-x.
8
CAR T-cell immunotherapy as the next horizon in cancer eradication: current landscape, challenges, and future directions.嵌合抗原受体T细胞免疫疗法作为癌症根除的新希望：现状、挑战与未来方向
Med Oncol. 2025 Aug 6;42(9):410. doi: 10.1007/s12032-025-02957-1.
9
Knowledge-map and bibliometric analysis of scientific research on FDA-approved Chimeric Antigen Receptor T cell products (2015-2024).美国食品药品监督管理局（FDA）批准的嵌合抗原受体T细胞产品的科学研究知识图谱与文献计量分析（2015 - 2024年）
Discov Oncol. 2025 Aug 3;16(1):1461. doi: 10.1007/s12672-025-03360-y.
10
Research progress on chimeric antigen receptor-based immunotherapy against autoimmune diseases.基于嵌合抗原受体的自身免疫性疾病免疫治疗研究进展
Hum Vaccin Immunother. 2025 Dec;21(1):2538350. doi: 10.1080/21645515.2025.2538350. Epub 2025 Aug 1.
本文引用的文献
1
Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis.抗 GD2 CAR-NKT 细胞治疗复发或难治性神经母细胞瘤的初步临床研究
Nat Med. 2020 Nov;26(11):1686-1690. doi: 10.1038/s41591-020-1074-2. Epub 2020 Oct 12.
2
Single-Cell Analyses Identify Brain Mural Cells Expressing CD19 as Potential Off-Tumor Targets for CAR-T Immunotherapies.单细胞分析鉴定出表达 CD19 的脑壁细胞，可能成为 CAR-T 免疫疗法的肿瘤外靶点。
Cell. 2020 Oct 1;183(1):126-142.e17. doi: 10.1016/j.cell.2020.08.022. Epub 2020 Sep 21.
3
Sleeping Beauty-engineered CAR T cells achieve antileukemic activity without severe toxicities.经基因编辑的 CAR T 细胞睡眠美人实现抗白血病活性而无严重毒性。
J Clin Invest. 2020 Nov 2;130(11):6021-6033. doi: 10.1172/JCI138473.
4
Chimeric Antigen Receptor Designed to Prevent Ubiquitination and Downregulation Showed Durable Antitumor Efficacy.旨在防止泛素化和下调的嵌合抗原受体显示出持久的抗肿瘤疗效。
Immunity. 2020 Aug 18;53(2):456-470.e6. doi: 10.1016/j.immuni.2020.07.011. Epub 2020 Aug 5.
5
A Distinct Transcriptional Program in Human CAR T Cells Bearing the 4-1BB Signaling Domain Revealed by scRNA-Seq.单细胞 RNA 测序揭示了携带 4-1BB 信号结构域的人 CAR T 细胞中独特的转录程序。
Mol Ther. 2020 Dec 2;28(12):2577-2592. doi: 10.1016/j.ymthe.2020.07.023. Epub 2020 Jul 25.
6
Multiple Signaling Roles of CD3ε and Its Application in CAR-T Cell Therapy.CD3ε 的多重信号作用及其在 CAR-T 细胞治疗中的应用。
Cell. 2020 Aug 20;182(4):855-871.e23. doi: 10.1016/j.cell.2020.07.018. Epub 2020 Jul 29.
7
Noncanonical binding of Lck to CD3ε promotes TCR signaling and CAR function.非规范的 Lck 与 CD3ε 结合促进 TCR 信号转导和 CAR 功能。
Nat Immunol. 2020 Aug;21(8):902-913. doi: 10.1038/s41590-020-0732-3. Epub 2020 Jul 20.
8
Iron chelation rescues hemolytic anemia and skin photosensitivity in congenital erythropoietic porphyria.铁螯合疗法可挽救先天性红细胞生成性卟啉症的溶血性贫血和皮肤光敏性。
Blood. 2020 Nov 19;136(21):2457-2468. doi: 10.1182/blood.2020006037.
9
Development of CAR-T cell therapies for multiple myeloma.嵌合抗原受体 T 细胞疗法治疗多发性骨髓瘤的研究进展。
Leukemia. 2020 Sep;34(9):2317-2332. doi: 10.1038/s41375-020-0930-x. Epub 2020 Jun 22.
10
Human chimeric antigen receptor macrophages for cancer immunotherapy.用于癌症免疫疗法的人嵌合抗原受体巨噬细胞。
Nat Biotechnol. 2020 Aug;38(8):947-953. doi: 10.1038/s41587-020-0462-y. Epub 2020 Mar 23.
Zotero 插件