• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

基于嵌合抗原受体 T 淋巴细胞的细胞疗法;自杀基因在机制论证、应用和生物安全性增强方面的作用:消除副作用的新机遇。

CAR-T lymphocyte-based cell therapies; mechanistic substantiation, applications and biosafety enhancement with suicide genes: new opportunities to melt side effects.

机构信息

ETSIAAB, Universidad Politécnica de Madrid, Madrid, Spain.

Laboratorio Cancer Stem Cell, HST group, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Madrid, Spain.

出版信息

Front Immunol. 2024 Jul 18;15:1333150. doi: 10.3389/fimmu.2024.1333150. eCollection 2024.

DOI:10.3389/fimmu.2024.1333150
PMID:39091493
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11291200/
Abstract

Immunotherapy has made significant strides in cancer treatment with strategies like checkpoint blockade antibodies and adoptive T cell transfer. Chimeric antigen receptor T cells (CAR-T) have emerged as a promising approach to combine these strategies and overcome their limitations. This review explores CAR-T cells as a living drug for cancer treatment. CAR-T cells are genetically engineered immune cells designed to target and eliminate tumor cells by recognizing specific antigens. The study involves a comprehensive literature review on CAR-T cell technology, covering structure optimization, generations, manufacturing processes, and gene therapy strategies. It examines CAR-T therapy in haematologic cancers and solid tumors, highlighting challenges and proposing a suicide gene-based mechanism to enhance safety. The results show significant advancements in CAR-T technology, particularly in structure optimization and generation. The manufacturing process has improved for broader clinical application. However, a series of inherent challenges and side effects still need to be addressed. In conclusion, CAR-T cells hold great promise for cancer treatment, but ongoing research is crucial to improve efficacy and safety for oncology patients. The proposed suicide gene-based mechanism offers a potential solution to mitigate side effects including cytokine release syndrome (the most common toxic side effect of CAR-T therapy) and the associated neurotoxicity.

摘要

免疫疗法在癌症治疗方面取得了重大进展,策略包括检查点阻断抗体和过继性 T 细胞转移。嵌合抗原受体 T 细胞(CAR-T)作为一种结合这些策略并克服其局限性的有前途的方法已经出现。本综述探讨了 CAR-T 细胞作为治疗癌症的活药物。CAR-T 细胞是经过基因工程改造的免疫细胞,通过识别特定抗原来靶向和消除肿瘤细胞。这项研究涉及对 CAR-T 细胞技术的全面文献回顾,涵盖结构优化、代际、制造工艺和基因治疗策略。它检查了 CAR-T 疗法在血液癌症和实体肿瘤中的应用,强调了挑战,并提出了一种基于自杀基因的机制来提高安全性。结果表明,CAR-T 技术取得了重大进展,特别是在结构优化和代际方面。制造工艺的改进使其更广泛地应用于临床。然而,仍需要解决一系列固有的挑战和副作用。总之,CAR-T 细胞在癌症治疗方面具有巨大的潜力,但需要开展进一步的研究来提高肿瘤患者的疗效和安全性。所提出的基于自杀基因的机制为减轻副作用提供了一种潜在的解决方案,包括细胞因子释放综合征(CAR-T 治疗最常见的毒性副作用)和相关的神经毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/cb3bf6a57670/fimmu-15-1333150-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/d1afc4ea55d3/fimmu-15-1333150-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/84ad0daed6a8/fimmu-15-1333150-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/7e07de36c19e/fimmu-15-1333150-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/c5a33a20982c/fimmu-15-1333150-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/0dc2f08f6197/fimmu-15-1333150-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/282d1042fe0f/fimmu-15-1333150-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/9f0cf727635b/fimmu-15-1333150-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/5a552df6c870/fimmu-15-1333150-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/8be9ec58ba11/fimmu-15-1333150-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/e62a6afa692c/fimmu-15-1333150-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/fb126f3dfa6b/fimmu-15-1333150-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/c22564976e27/fimmu-15-1333150-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/5e39e1e0a0c5/fimmu-15-1333150-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/cb3bf6a57670/fimmu-15-1333150-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/d1afc4ea55d3/fimmu-15-1333150-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/84ad0daed6a8/fimmu-15-1333150-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/7e07de36c19e/fimmu-15-1333150-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/c5a33a20982c/fimmu-15-1333150-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/0dc2f08f6197/fimmu-15-1333150-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/282d1042fe0f/fimmu-15-1333150-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/9f0cf727635b/fimmu-15-1333150-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/5a552df6c870/fimmu-15-1333150-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/8be9ec58ba11/fimmu-15-1333150-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/e62a6afa692c/fimmu-15-1333150-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/fb126f3dfa6b/fimmu-15-1333150-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/c22564976e27/fimmu-15-1333150-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/5e39e1e0a0c5/fimmu-15-1333150-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe26/11291200/cb3bf6a57670/fimmu-15-1333150-g014.jpg

相似文献

1
CAR-T lymphocyte-based cell therapies; mechanistic substantiation, applications and biosafety enhancement with suicide genes: new opportunities to melt side effects.基于嵌合抗原受体 T 淋巴细胞的细胞疗法;自杀基因在机制论证、应用和生物安全性增强方面的作用:消除副作用的新机遇。
Front Immunol. 2024 Jul 18;15:1333150. doi: 10.3389/fimmu.2024.1333150. eCollection 2024.
2
Advancements and challenges in developing in vivo CAR T cell therapies for cancer treatment.开发用于癌症治疗的体内 CAR T 细胞疗法的进展和挑战。
EBioMedicine. 2024 Aug;106:105266. doi: 10.1016/j.ebiom.2024.105266. Epub 2024 Aug 1.
3
Immune Cell Hacking: Challenges and Clinical Approaches to Create Smarter Generations of Chimeric Antigen Receptor T Cells.免疫细胞改造:创造更智能嵌合抗原受体 T 细胞的挑战和临床方法。
Front Immunol. 2018 Jul 31;9:1717. doi: 10.3389/fimmu.2018.01717. eCollection 2018.
4
CAR T Cells Redirected to CD44v6 Control Tumor Growth in Lung and Ovary Adenocarcinoma Bearing Mice.嵌合抗原受体 T 细胞靶向 CD44v6 控制肺和卵巢腺癌荷瘤小鼠的肿瘤生长。
Front Immunol. 2020 Feb 4;11:99. doi: 10.3389/fimmu.2020.00099. eCollection 2020.
5
ReCARving the future: bridging CAR T-cell therapy gaps with synthetic biology, engineering, and economic insights.重塑未来:利用合成生物学、工程学和经济学的洞见,弥合 CAR T 细胞治疗的差距。
Front Immunol. 2024 Sep 5;15:1432799. doi: 10.3389/fimmu.2024.1432799. eCollection 2024.
6
Reformation in chimeric antigen receptor based cancer immunotherapy: Redirecting natural killer cell.嵌合抗原受体肿瘤免疫治疗的改革:重定向自然杀伤细胞。
Biochim Biophys Acta Rev Cancer. 2018 Apr;1869(2):200-215. doi: 10.1016/j.bbcan.2018.01.005. Epub 2018 Jan 31.
7
Future perspectives on engineered T cells for cancer.工程化 T 细胞治疗癌症的未来展望。
Trends Cancer. 2024 Aug;10(8):687-695. doi: 10.1016/j.trecan.2024.05.007. Epub 2024 Jun 8.
8
Chimeric antigen-receptor T-cell therapy for hematological malignancies and solid tumors: Clinical data to date, current limitations and perspectives.嵌合抗原受体 T 细胞疗法治疗血液系统恶性肿瘤和实体瘤:临床数据现状、当前局限性和展望。
Curr Res Transl Med. 2017 Sep;65(3):93-102. doi: 10.1016/j.retram.2017.08.003.
9
Chimeric antigen receptor-engineered T-cell therapy for liver cancer.嵌合抗原受体修饰的 T 细胞治疗肝癌。
Hepatobiliary Pancreat Dis Int. 2018 Aug;17(4):301-309. doi: 10.1016/j.hbpd.2018.05.005. Epub 2018 May 24.
10
A new insight in chimeric antigen receptor-engineered T cells for cancer immunotherapy.嵌合抗原受体工程化T细胞用于癌症免疫治疗的新见解。
J Hematol Oncol. 2017 Jan 3;10(1):1. doi: 10.1186/s13045-016-0379-6.

引用本文的文献

1
STAT3 Signaling Pathway in Health and Disease.健康与疾病中的信号转导和转录激活因子3(STAT3)信号通路
MedComm (2020). 2025 Mar 30;6(4):e70152. doi: 10.1002/mco2.70152. eCollection 2025 Apr.

本文引用的文献

1
Emerging Strategies to Overcome Current CAR-T Therapy Dilemmas - Exosomes Derived from CAR-T Cells.克服当前 CAR-T 疗法困境的新兴策略 - CAR-T 细胞衍生的外泌体。
Int J Nanomedicine. 2024 Mar 18;19:2773-2791. doi: 10.2147/IJN.S445101. eCollection 2024.
2
Recent progress in chimeric antigen receptor therapy for acute myeloid leukemia.急性髓系白血病嵌合抗原受体疗法的最新进展
Ann Hematol. 2024 Jun;103(6):1843-1857. doi: 10.1007/s00277-023-05601-y. Epub 2024 Feb 21.
3
Ocular toxicities in chimeric antigen receptor T-cell therapy: a real-world study leveraging FAERS database.
嵌合抗原受体 T 细胞治疗中的眼毒性:利用 FAERS 数据库进行的真实世界研究。
Immunotherapy. 2024 Feb;16(3):161-172. doi: 10.2217/imt-2023-0220. Epub 2023 Dec 21.
4
PGE2-EP4 signaling steers cDC2 maturation toward the induction of suppressive T-cell responses.前列腺素E2-EP4信号传导引导cDC2成熟,以诱导抑制性T细胞反应。
Eur J Immunol. 2024 Mar;54(3):e2350770. doi: 10.1002/eji.202350770. Epub 2024 Jan 8.
5
Aldehyde dehydrogenase 2-mediated aldehyde metabolism promotes tumor immune evasion by regulating the NOD/VISTA axis.醛脱氢酶 2 介导的醛代谢通过调节 NOD/VISTA 轴促进肿瘤免疫逃逸。
J Immunother Cancer. 2023 Dec 7;11(12):e007487. doi: 10.1136/jitc-2023-007487.
6
Kindlin-2 regulates colonic cancer stem-like cells survival and self-renewal via Wnt/β-catenin mediated pathway.Kindlin-2 通过 Wnt/β-catenin 介导的途径调节结肠癌细胞干性样细胞的存活和自我更新。
Cell Signal. 2024 Jan;113:110953. doi: 10.1016/j.cellsig.2023.110953. Epub 2023 Oct 29.
7
Immunotherapies inducing immunogenic cell death in cancer: insight of the innate immune system.诱导肿瘤发生免疫原性细胞死亡的免疫疗法:固有免疫系统的见解。
Front Immunol. 2023 Nov 23;14:1294434. doi: 10.3389/fimmu.2023.1294434. eCollection 2023.
8
Immune checkpoints are predominantly co-expressed by clonally expanded CD4FoxP3 intratumoral T-cells in primary human cancers.免疫检查点主要由原发性人类癌症中克隆扩增的 CD4FoxP3 肿瘤内 T 细胞共表达。
J Exp Clin Cancer Res. 2023 Dec 6;42(1):333. doi: 10.1186/s13046-023-02897-6.
9
Loss of CD20 expression as a mechanism of resistance to mosunetuzumab in relapsed/refractory B-cell lymphomas.CD20 表达缺失是复发/难治性 B 细胞淋巴瘤对 mosunetuzumab 产生耐药的机制。
Blood. 2024 Feb 29;143(9):822-832. doi: 10.1182/blood.2023022348.
10
Self-Renewal Inhibition in Breast Cancer Stem Cells: Moonlight Role of PEDF in Breast Cancer.乳腺癌干细胞中的自我更新抑制:PEDF在乳腺癌中的“兼职”作用
Cancers (Basel). 2023 Nov 15;15(22):5422. doi: 10.3390/cancers15225422.