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文献精选 > 近年高分"CAR-T疗法"研究（IF≥30，近5年）

CAR T therapy beyond cancer: the evolution of a living drug. ​

文献信息 ​

DOI10.1038/s41586-023-06243-w
PMID37495877
期刊Nature
影响因子48.5
JCR 分区Q1
发表年份2023
被引次数165
关键词CAR T疗法, 肿瘤免疫治疗, 自体T细胞, 非肿瘤疾病, 安全性
文献类型Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural
ISSN0028-0836
页码707-715
期号619(7971)
作者Daniel J Baker, Zoltan Arany, Joseph A Baur, Jonathan A Epstein, Carl H June

一句话小结 ​

本研究回顾了CAR T细胞疗法在血液癌症治疗中取得的成功，并探讨其在自身免疫、慢性感染等非癌症疾病中的应用潜力和面临的挑战，强调了新技术对其发展的重要性。研究结果为CAR T疗法的广泛应用提供了新的视角，同时也提出了对特异性和安全性的关注。

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CAR T疗法 · 肿瘤免疫治疗 · 自体T细胞 · 非肿瘤疾病 · 安全性

摘要 ​

工程化患者自身的T细胞，以选择性靶向和消灭肿瘤细胞，已成功治愈了无法治疗的血液癌症患者。这些结果激励了该领域将嵌合抗原受体（CAR）T疗法推广到整个肿瘤学。然而，临床和前临床研究的证据强调了CAR T疗法在治疗自身免疫、慢性感染、心脏纤维化、衰老相关疾病及其他病症方面的潜力。同时，新技术和平台的应用为CAR T疗法在非癌症病理中的应用提供了进一步的机会。在这里，我们回顾了CAR T疗法的理论基础、肿瘤学中面临的当前挑战、非癌症疾病初步报告的概述以及相关新兴技术的讨论。我们考察了该疗法在广泛背景下的潜在应用。最后，我们强调了关于特异性和安全性的担忧，并概述了CAR T疗法在癌症之外的发展路径。

英文摘要 ​

Engineering a patient's own T cells to selectively target and eliminate tumour cells has cured patients with untreatable haematologic cancers. These results have energized the field to apply chimaeric antigen receptor (CAR) T therapy throughout oncology. However, evidence from clinical and preclinical studies underscores the potential of CAR T therapy beyond oncology in treating autoimmunity, chronic infections, cardiac fibrosis, senescence-associated disease and other conditions. Concurrently, the deployment of new technologies and platforms provides further opportunity for the application of CAR T therapy to noncancerous pathologies. Here we review the rationale behind CAR T therapy, current challenges faced in oncology, a synopsis of preliminary reports in noncancerous diseases, and a discussion of relevant emerging technologies. We examine potential applications for this therapy in a wide range of contexts. Last, we highlight concerns regarding specificity and safety and outline the path forward for CAR T therapy beyond cancer.

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主要研究问题 ​

  1. CAR T疗法在治疗自身免疫性疾病时面临哪些具体挑战？
  2. 目前有哪些新兴技术可以提高CAR T疗法在非肿瘤疾病中的应用效果？
  3. CAR T疗法在慢性感染治疗中的成功案例有哪些，它们的机制是什么？
  4. 针对心脏纤维化，CAR T疗法的研究进展如何，未来的应用前景如何？
  5. 如何评估CAR T疗法在非癌症病症中的安全性和特异性问题？

核心洞察 ​

研究背景和目的 ​

CAR T细胞疗法通过工程化患者自身的T细胞，选择性地靶向并消除肿瘤细胞，已成功治愈了多例难治性血液癌症患者。这一成功激励了该领域将CAR T疗法推广至整个肿瘤学。然而，临床和前临床研究的证据表明，CAR T疗法在治疗自身免疫性疾病、慢性感染、心脏纤维化、衰老相关疾病及其他病症方面也具有潜力。本研究旨在探讨CAR T疗法的合理性、在肿瘤学面临的挑战、非癌症疾病的初步报告及相关新兴技术。

主要方法/材料/实验设计 ​

本研究采用文献综述的方法，系统回顾了CAR T疗法的应用现状及未来方向。主要步骤如下：

Mermaid diagram
  • 文献回顾：收集和分析相关文献，形成对CAR T疗法的全面理解。
  • CAR T疗法的合理性：探讨其在不同病理状态下的应用基础。
  • 肿瘤学中的挑战：总结当前CAR T疗法在肿瘤治疗中遇到的主要问题。
  • 非癌症疾病的初步报告：概述已有的非肿瘤应用案例及其效果。
  • 新兴技术的讨论：评估新技术如何促进CAR T疗法的发展。
  • 安全性和特异性问题：讨论CAR T疗法的潜在风险。
  • 未来发展方向：提出CAR T疗法在非癌症领域的应用前景。

关键结果和发现 ​

  1. 肿瘤学中的挑战：

    • CAR T疗法的有效性受限于肿瘤微环境的抑制作用。
    • 特异性识别和副作用管理仍需改进。

  2. 非癌症疾病的初步报告：

    • 现有研究表明，CAR T疗法在自身免疫性疾病和慢性感染中的应用显示出积极前景。
    • 相关技术如基因编辑和细胞工程的进步，为CAR T疗法的扩展提供了新的可能性。

主要结论/意义/创新性 ​

本研究表明，CAR T疗法不仅限于肿瘤治疗，还可以应用于多种非癌症疾病。随着新技术的发展，CAR T疗法的安全性和特异性问题有望得到解决。这为未来在自身免疫性疾病、慢性感染等领域的治疗提供了新的思路和可能性，具有重要的临床意义和创新性。

研究局限性和未来方向 ​

  • 局限性：

    • 当前非癌症领域的临床研究仍较为有限，缺乏大规模随机对照试验的数据支持。
    • 安全性和长期效果的评估尚不充分。

  • 未来方向：

    • 需要更多的临床试验来验证CAR T疗法在非癌症领域的有效性和安全性。
    • 探索与其他治疗手段的联合应用，以提高疗效和降低副作用。
    • 加强对CAR T细胞特异性和持久性的研究，以提升治疗的安全性和有效性。

参考文献 ​

  1. 'Off-the-shelf' allogeneic CAR T cells: development and challenges. - S Depil;P Duchateau;S A Grupp;G Mufti;L Poirot - Nature reviews. Drug discovery (2020)
  2. An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors. - Katharina Reinhard;Benjamin Rengstl;Petra Oehm;Kristina Michel;Arne Billmeier;Nina Hayduk;Oliver Klein;Kathrin Kuna;Yasmina Ouchan;Stefan Wöll;Elmar Christ;David Weber;Martin Suchan;Thomas Bukur;Matthias Birtel;Veronika Jahndel;Karolina Mroz;Kathleen Hobohm;Lena Kranz;Mustafa Diken;Klaus Kühlcke;Özlem Türeci;Ugur Sahin - Science (New York, N.Y.) (2020)
  3. Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours. - Christian L Flugel;Robbie G Majzner;Giedre Krenciute;Gianpietro Dotti;Stanley R Riddell;Dimitrios L Wagner;Mohamed Abou-El-Enein - Nature reviews. Clinical oncology (2023)
  4. Targeting of human immunodeficiency virus-infected cells by CD8+ T lymphocytes armed with universal T-cell receptors. - M R Roberts;L Qin;D Zhang;D H Smith;A C Tran;T J Dull;J E Groopman;D J Capon;R A Byrn;M H Finer - Blood (1994)
  5. Thermogenic T cells: a cell therapy for obesity? - Ulf H Beier;Daniel J Baker;Joseph A Baur - American journal of physiology. Cell physiology (2022)
  6. Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast Cancer. - Julia Tchou;Yangbing Zhao;Bruce L Levine;Paul J Zhang;Megan M Davis;Jan Joseph Melenhorst;Irina Kulikovskaya;Andrea L Brennan;Xiaojun Liu;Simon F Lacey;Avery D Posey;Austin D Williams;Alycia So;Jose R Conejo-Garcia;Gabriela Plesa;Regina M Young;Shannon McGettigan;Jean Campbell;Robert H Pierce;Jennifer M Matro;Angela M DeMichele;Amy S Clark;Laurence J Cooper;Lynn M Schuchter;Robert H Vonderheide;Carl H June - Cancer immunology research (2017)
  7. Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies. - Reuben Benjamin;Charlotte Graham;Deborah Yallop;Agnieszka Jozwik;Oana C Mirci-Danicar;Giovanna Lucchini;Danielle Pinner;Nitin Jain;Hagop Kantarjian;Nicolas Boissel;Marcela V Maus;Matthew J Frigault;André Baruchel;Mohamad Mohty;Athos Gianella-Borradori;Florence Binlich;Svetlana Balandraud;Fabien Vitry;Elisabeth Thomas;Anne Philippe;Sylvain Fouliard;Sandra Dupouy;Ibtissam Marchiq;Maria Almena-Carrasco;Nicolas Ferry;Sylvain Arnould;Cyril Konto;Paul Veys;Waseem Qasim; - Lancet (London, England) (2020)
  8. CAR T therapy extends its reach to autoimmune diseases. - Daniel J Baker;Carl H June - Cell (2022)
  9. Engineering Antibodies Targeting p16 MHC-Peptide Complexes. - Nicholas J Rettko;Judith Campisi;James A Wells - ACS chemical biology (2022)
  10. Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice. - Masayoshi Suda;Ippei Shimizu;Goro Katsuumi;Yohko Yoshida;Yuka Hayashi;Ryutaro Ikegami;Naomi Matsumoto;Yutaka Yoshida;Ryuta Mikawa;Akihiro Katayama;Jun Wada;Masahide Seki;Yutaka Suzuki;Atsushi Iwama;Hironori Nakagami;Ayako Nagasawa;Ryuichi Morishita;Masataka Sugimoto;Shujiro Okuda;Masanori Tsuchida;Kazuyuki Ozaki;Mayumi Nakanishi-Matsui;Tohru Minamino - Nature aging (2021)

引用本文的文献 ​

  1. LIGHTing CAR T in the tumor microenvironment. - Yong Liang;Yang-Xin Fu - Molecular therapy : the journal of the American Society of Gene Therapy (2023)
  2. Recombinant oncolytic adenovirus armed with CCL5, IL-12, and IFN-γ promotes CAR-T infiltration and proliferation in vivo to eradicate local and distal tumors. - Lin Fang;Sen Yuan;Meng Wang;Chen Zhang;Xueyan Wang;Hailong Li;Jie Yang;Wanjing Li;Nan Sun;Qi Zhang;Yuxin Zhang;Dafei Chai;Huizhong Li;Junnian Zheng;Gang Wang - Cell death discovery (2023)
  3. CAR-NK Cells Generated with mRNA-LNPs Kill Tumor Target Cells In Vitro and In Vivo. - Vita Golubovskaya;John Sienkiewicz;Jinying Sun;Shiming Zhang;Yanwei Huang;Hua Zhou;Hizkia Harto;Shirley Xu;Robert Berahovich;Lijun Wu - International journal of molecular sciences (2023)
  4. A Genetically Encoded Dark-to-Bright Biosensor for Visualisation of Granzyme-Mediated Cytotoxicity. - Christopher Bednar;Sabrina Kübel;Arne Cordsmeier;Brigitte Scholz;Hanna Menschikowski;Armin Ensser - International journal of molecular sciences (2023)
  5. Advances in CAR-Engineered Immune Cell Generation: Engineering Approaches and Sourcing Strategies. - Zhaozhao Chen;Yu Hu;Heng Mei - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
  6. CAR-T Cell Therapy: From the Shop to Cancer Therapy. - Ashanti Concepción Uscanga-Palomeque;Ana Karina Chávez-Escamilla;Cynthia Aracely Alvizo-Báez;Santiago Saavedra-Alonso;Luis Daniel Terrazas-Armendáriz;Reyes S Tamez-Guerra;Cristina Rodríguez-Padilla;Juan Manuel Alcocer-González - International journal of molecular sciences (2023)
  7. Chimeric antigen receptor T cell therapy: a new emerging landscape in autoimmune rheumatic diseases. - Xia Lyu;Latika Gupta;Eleni Tholouli;Hector Chinoy - Rheumatology (Oxford, England) (2024)
  8. Recruiting In Vitro Transcribed mRNA against Cancer Immunotherapy: A Contemporary Appraisal of the Current Landscape. - Androulla N Miliotou;Sofia K Georgiou-Siafis;Charikleia Ntenti;Ioannis S Pappas;Lefkothea C Papadopoulou - Current issues in molecular biology (2023)
  9. Rationally designed approaches to augment CAR-T therapy for solid tumor treatment. - Chaojie Zhu;Qing Wu;Tao Sheng;Jiaqi Shi;Xinyuan Shen;Jicheng Yu;Yang Du;Jie Sun;Tingxizi Liang;Kaixin He;Yuan Ding;Hongjun Li;Zhen Gu;Weilin Wang - Bioactive materials (2024)
  10. The expanded application of CAR-T cell therapy for the treatment of multiple non-tumoral diseases. - Zhuoqun Liu;Yuchen Xiao;Jianjun Lyu;Duohui Jing;Liu Liu;Yanbin Fu;Wenxin Niu;Lingjing Jin;Chao Zhang - Protein & cell (2024)

... (155 更多 篇文献)

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