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Advances in Universal CAR-T Cell Therapy. ​

文献信息 ​

DOI10.3389/fimmu.2021.744823
PMID34691052
期刊Frontiers in immunology
影响因子5.9
JCR 分区Q1
发表年份2021
被引次数102
关键词CRISPR/Cas9, 细胞免疫疗法, 嵌合抗原受体T细胞疗法, 基因编辑, 通用嵌合抗原受体T细胞疗法
文献类型Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN1664-3224
页码744823
期号12()
作者Haolong Lin, Jiali Cheng, Wei Mu, Jianfeng Zhou, Li Zhu

一句话小结 ​

本研究回顾了嵌合抗原受体T细胞（CAR-T）疗法在抗肿瘤治疗中的进展与挑战，重点讨论了普适性CAR-T（UCAR-T）细胞疗法的潜在优势，包括降低成本和缩短生产周期。通过比较UCAR-T与传统CAR-T的安全性和有效性，本文为未来UCAR-T疗法的发展提供了重要见解，并探讨了其他免疫细胞作为UCAR-T的补充的可能性。

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CRISPR/Cas9 · 细胞免疫疗法 · 嵌合抗原受体T细胞疗法 · 基因编辑 · 通用嵌合抗原受体T细胞疗法

摘要 ​

嵌合抗原受体T细胞（CAR-T）疗法在抗肿瘤治疗方面取得了卓越的成就，尤其在血液恶性肿瘤的治疗中，展现出显著的长期抗肿瘤效果和更高的靶向特异性。然而，自体CAR-T细胞疗法仍存在一些限制，如高昂的费用、较长的制造周期以及受限的细胞来源。开发普适性CAR-T（UCAR-T）细胞疗法是一个有吸引力的突破点，可能克服大部分这些缺陷。在此，我们回顾了CAR-T细胞疗法的进展和挑战，特别关注UCAR-T细胞疗法与原始CAR-T细胞疗法的全面比较。此外，我们总结了UCAR-T细胞疗法的安全性和有效性方面的发展与关注。最后，我们讨论了其他免疫细胞，这些细胞可能作为UCAR-T细胞的补充，成为有前景的候选者。通过详细概述，我们描述了当前的研究现状，并探讨了UCAR-T细胞疗法的前景。

英文摘要 ​

Chimeric antigen receptor T (CAR-T) cell therapy achieved extraordinary achievements results in antitumor treatments, especially against hematological malignancies, where it leads to remarkable, long-term antineoplastic effects with higher target specificity. Nevertheless, some limitations persist in autologous CAR-T cell therapy, such as high costs, long manufacturing periods, and restricted cell sources. The development of a universal CAR-T (UCAR-T) cell therapy is an attractive breakthrough point that may overcome most of these drawbacks. Here, we review the progress and challenges in CAR-T cell therapy, especially focusing on comprehensive comparison in UCAR-T cell therapy to original CAR-T cell therapy. Furthermore, we summarize the developments and concerns about the safety and efficiency of UCAR-T cell therapy. Finally, we address other immune cells, which might be promising candidates as a complement for UCAR-T cells. Through a detailed overview, we describe the current landscape and explore the prospect of UCAR-T cell therapy.

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主要研究问题 ​

  1. UCAR-T细胞治疗在不同类型肿瘤中的应用效果如何？
  2. 在成本和生产周期方面，UCAR-T细胞治疗相比于自体CAR-T细胞治疗有哪些具体优势？
  3. UCAR-T细胞治疗的安全性和有效性评估标准是什么？
  4. 除了UCAR-T细胞，还有哪些免疫细胞可能作为肿瘤治疗的补充疗法？
  5. 当前UCAR-T细胞治疗的主要挑战和未来发展方向是什么？

核心洞察 ​

研究背景和目的 ​

CAR-T细胞疗法在抗肿瘤治疗中取得了显著成就，尤其是在血液恶性肿瘤方面。然而，自体CAR-T细胞疗法仍面临高成本、生产周期长和细胞来源受限等局限性。因此，开发通用CAR-T（UCAR-T）细胞疗法被认为是克服这些缺陷的重要突破点。本文综述了CAR-T细胞疗法的进展与挑战，重点比较了UCAR-T细胞疗法与传统CAR-T细胞疗法的差异，探讨了UCAR-T细胞的安全性和有效性发展，以及其他免疫细胞作为UCAR-T细胞的补充候选者的前景。

主要方法/材料/实验设计 ​

本文采用文献综述的方法，对UCAR-T细胞疗法的最新进展进行了全面的分析。主要的技术路线包括以下几个步骤：

Mermaid diagram

关键结果和发现 ​

  1. UCAR-T细胞的优势：UCAR-T细胞可以来自健康供体，降低了制造成本，缩短了生产周期，并且可以大规模生产，提高了可及性。
  2. 临床试验结果：UCART19的临床试验显示，在复发或难治性B细胞急性淋巴细胞白血病患者中，有67%的患者在28天内达到了完全缓解。
  3. 安全性问题：UCAR-T细胞治疗仍面临与传统CAR-T细胞相似的安全性风险，包括细胞因子释放综合症（CRS）和神经毒性，但通过基因编辑等技术可以减少这些风险。

主要结论/意义/创新性 ​

UCAR-T细胞疗法的开发代表了CAR-T细胞疗法的重大进步，能够显著提高治疗的可及性和适用性。通过基因编辑技术，UCAR-T细胞能够克服传统CAR-T细胞疗法中的一些安全性和有效性问题，具有成为“随用随取”的治疗方法的潜力，推动了细胞免疫疗法的发展。

研究局限性和未来方向 ​

  1. 研究局限性：目前UCAR-T细胞的持久性仍低于自体CAR-T细胞，临床试验数据有限，特别是在固体肿瘤的应用方面。
  2. 未来方向：未来的研究将集中在提高UCAR-T细胞的持久性、降低免疫原性、扩大适应症范围以及探索其他类型的细胞（如NK细胞、iPSC等）作为UCAR-T细胞的替代或补充方案。

通过对UCAR-T细胞疗法的深入研究，期望能够实现更广泛的抗肿瘤治疗应用，为患者提供更为有效和安全的治疗选择。

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引用本文的文献 ​

  1. Targeting BCMA to Treat Multiple Myeloma: Updates From the 2021 ASH Annual Meeting. - Ruiting Guo;Wenyi Lu;Yi Zhang;Xinping Cao;Xin Jin;Mingfeng Zhao - Frontiers in immunology (2022)
  2. Donor T cells for CAR T cell therapy. - Tiffany C Y Tang;Ning Xu;Robert Nordon;Michelle Haber;Kenneth Micklethwaite;Alla Dolnikov - Biomarker research (2022)
  3. Hurdles to breakthrough in CAR T cell therapy of solid tumors. - Faroogh Marofi;Harun Achmad;Dmitry Bokov;Walid Kamal Abdelbasset;Zeid Alsadoon;Supat Chupradit;Wanich Suksatan;Siavash Shariatzadeh;Zahra Hasanpoor;Mahboubeh Yazdanifar;Navid Shomali;Farhad Motavalli Khiavi - Stem cell research & therapy (2022)
  4. A Bibliometric and Knowledge-Map Analysis of CAR-T Cells From 2009 to 2021. - Lele Miao;Juan Zhang;Zhengchao Zhang;Song Wang;Futian Tang;Muzhou Teng;Yumin Li - Frontiers in immunology (2022)
  5. Pharmacotherapeutic Treatment of Glioblastoma: Where Are We to Date? - Lidia Gatto;Vincenzo Di Nunno;Enrico Franceschi;Alicia Tosoni;Stefania Bartolini;Alba Ariela Brandes - Drugs (2022)
  6. Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy. - Weijie Cao;Haizhou Xing;Yingmei Li;Wenliang Tian;Yongping Song;Zhongxing Jiang;Jifeng Yu - Biomarker research (2022)
  7. Efficacy and safety of CD19 CAR-T cell therapy for acute lymphoblastic leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation. - Xing-Yu Cao;Jing-Jing Li;Pei-Hua Lu;Kai-Yan Liu - International journal of hematology (2022)
  8. Influence of Culture Conditions on Ex Vivo Expansion of T Lymphocytes and Their Function for Therapy: Current Insights and Open Questions. - Harish Sudarsanam;Raymund Buhmann;Reinhard Henschler - Frontiers in bioengineering and biotechnology (2022)
  9. Immunogenic Cell Death Enhances Immunotherapy of Diffuse Intrinsic Pontine Glioma: From Preclinical to Clinical Studies. - Guohao Liu;Yanmei Qiu;Po Zhang;Zirong Chen;Sui Chen;Weida Huang;Baofeng Wang;Xingjiang Yu;Dongsheng Guo - Pharmaceutics (2022)
  10. Current progress in CAR-T cell therapy for tumor treatment. - Lei Chen;Ting Xie;Bing Wei;Da-Lin Di - Oncology letters (2022)

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