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Overview of approved CAR-T therapies, ongoing clinical trials, and its impact on clinical practice. ​

文献信息 ​

DOI10.1002/jha2.338
PMID35844299
期刊EJHaem
影响因子1.2
JCR 分区Q4
发表年份2022
被引次数71
关键词CAR-T细胞治疗, 急性淋巴细胞白血病, 弥漫性大B细胞淋巴瘤, 多发性骨髓瘤, 非霍奇金淋巴瘤
文献类型Journal Article, Review
ISSN2688-6146
页码6-10
期号3(Suppl 1)
作者Salyka Sengsayadeth, Bipin N Savani, Olalekan Oluwole, Bhagirathbhai Dholaria

一句话小结 ​

近年来，CAR-T疗法在治疗恶性肿瘤方面取得显著进展，尤其是在非霍奇金淋巴瘤和B细胞急性淋巴细胞白血病中显示出高反应率和持久缓解，未来有望成为高等级B细胞淋巴瘤的主要治疗选择。该研究综述了现有CAR-T疗法及其未来在其他血液恶性肿瘤中的应用潜力，强调了新型抗原靶向治疗的意义。

在麦伴科研 (maltsci.com) 搜索更多文献 ​

CAR-T细胞治疗 · 急性淋巴细胞白血病 · 弥漫性大B细胞淋巴瘤 · 多发性骨髓瘤 · 非霍奇金淋巴瘤

摘要 ​

近年来，嵌合抗原受体T细胞（CAR-T）疗法在多种恶性肿瘤中迅速扩展。CAR-T疗法深刻改变了非霍奇金淋巴瘤、B细胞急性淋巴细胞白血病和多发性骨髓瘤的治疗格局。目前可用的CD19和B细胞成熟抗原导向的CAR-T疗法已在接受过标准疗法失败的患者中显示出高整体反应率和持久的缓解效果。多个研究正在进行中，探讨CAR-T细胞疗法作为早期治疗方案的作用。在高等级B细胞淋巴瘤中，CD19 CAR-T疗法可能在不久的将来取代自体造血细胞移植，成为第二线治疗。针对新型肿瘤相关抗原的CAR-T细胞疗法将有助于扩大该治疗模式在其他血液恶性肿瘤中的应用。它也可能有助于克服目前已批准的CAR-T细胞疗法的局限性。在本综述中，我们提供了当前已批准的CAR-T疗法的概述以及可能对临床实践产生影响的即将进行的临床试验。

英文摘要 ​

In recent years, we have seen rapid expansion of chimeric antigen receptor T-cell (CAR-T) therapies in multiple malignancies. CAR-T therapy has profoundly altered the treatment landscape of non-Hodgkin lymphoma, B-cell acute lymphoblastic leukemia, and multiple myeloma. Currently available CD19 and B-cell maturation antigen-directed CAR-T therapies have shown high overall response rate and durable remissions in patients who have failed standard therapies. Multiple studies are underway exploring the role of CAR-T-cell therapy as earlier line of treatment. In high-grade B-cell lymphoma, CD19 CAR-T therapy may replace autologous hematopoietic cell transplantation as second line therapy in near future. CAR-T-cell therapy targeting novel tumor-associated antigens will help expand utility of this treatment modality in other hematological malignancies. It may also help overcome limitations of currently approved CAR-T-cell therapies. In this review, we have provided an overview of currently approved CAR-T therapies and upcoming clinical trials which may potentially impact the clinical practice.

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主要研究问题 ​

  1. 当前有哪些新兴的CAR-T疗法正在进行临床试验，预期的疗效和安全性如何？
  2. 针对不同肿瘤类型的CAR-T疗法，未来的研究方向和挑战是什么？
  3. 如何评估CAR-T疗法在不同患者群体中的适应性和效果？
  4. CAR-T疗法在临床实践中对治疗方案的整合有何影响，是否会改变传统治疗模式？
  5. 在CAR-T疗法的开发中，针对新型肿瘤相关抗原的研究有哪些进展和前景？

核心洞察 ​

研究背景和目的 ​

近年来，嵌合抗原受体T细胞（CAR-T）疗法在多种恶性肿瘤的治疗中迅速发展，特别是在非霍奇金淋巴瘤、B细胞急性淋巴细胞白血病和多发性骨髓瘤等疾病中，CAR-T疗法显著改变了治疗格局。本文旨在概述目前已批准的CAR-T疗法、正在进行的临床试验及其对临床实践的影响。

主要方法/材料/实验设计 ​

本综述主要通过对已批准的CAR-T疗法的文献回顾，分析了其在不同恶性肿瘤中的应用。具体的技术路线如下：

Mermaid diagram

关键结果和发现 ​

  • 已批准的CAR-T疗法：

    • 目前有四种针对非霍奇金淋巴瘤的CAR-T产品，主要靶向CD19。
    • 这些疗法在治疗复发或难治性高等级血液恶性肿瘤患者中表现出高的总体反应率和持久的缓解。

  • 临床试验结果：

    • 例如，axi-cel在ZUMA-1试验中显示82%的总体反应率，54%的完全缓解率。
    • tisa-cel在儿童和年轻成人中治疗B-ALL时，3个月内81%的患者达到了完全缓解。

  • 新疗法开发：

    • 研究还在探索针对新肿瘤相关抗原的CAR-T疗法，以扩展其在其他血液恶性肿瘤中的应用。

主要结论/意义/创新性 ​

CAR-T疗法的快速发展为复发或难治性血液恶性肿瘤患者提供了新的治疗选择，显著改善了这些患者的预后。特别是在高风险的非霍奇金淋巴瘤和B细胞急性淋巴细胞白血病中，CAR-T疗法展现出优于传统治疗的疗效和安全性。此外，CAR-T疗法的创新靶点和组合疗法正在被广泛研究，可能会进一步提升治疗效果和患者生存率。

研究局限性和未来方向 ​

尽管CAR-T疗法在临床应用中取得了显著进展，但仍存在一些局限性，包括：

  • 治疗相关的毒性反应（如细胞因子释放综合症和神经毒性）需进一步优化管理。
  • 对于不同CAR-T产品在同一临床环境中的比较仍存在挑战。

未来的研究方向包括：

  • 探索多靶点CAR-T疗法以克服抗原逃逸问题。
  • 结合其他免疫调节剂和化疗药物以提高疗效和安全性。
  • 评估CAR-T疗法在早期治疗中的应用潜力，进一步改变临床实践模式。

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引用本文的文献 ​

  1. Targeting CD10 on B-Cell Leukemia Using the Universal CAR T-Cell Platform (UniCAR). - Nicola Mitwasi;Claudia Arndt;Liliana R Loureiro;Alexandra Kegler;Frederick Fasslrinner;Nicole Berndt;Ralf Bergmann;Vaclav Hořejší;Claudia Rössig;Michael Bachmann;Anja Feldmann - International journal of molecular sciences (2022)
  2. Overview of approved CAR-T therapies, ongoing clinical trials, and its impact on clinical practice. - Salyka Sengsayadeth;Bipin N Savani;Olalekan Oluwole;Bhagirathbhai Dholaria - EJHaem (2022)
  3. Chimeric antigen receptor-T cell therapies: The changing landscape. - Salyka M Sengsayadeth;Bhagirathbhai R Dholaria;Bipin N Savani;Olalekan O Oluwole - EJHaem (2022)
  4. Current updates on generations, approvals, and clinical trials of CAR T-cell therapy. - Tadesse Asmamaw Dejenie;Markeshaw Tiruneh G/Medhin;Gashaw Dessie Terefe;Fitalew Tadele Admasu;Wondwossen Wale Tesega;Endeshaw Chekol Abebe - Human vaccines & immunotherapeutics (2022)
  5. Mast Cells and Dendritic Cells as Cellular Immune Checkpoints in Immunotherapy of Solid Tumors. - Katerina Kalkusova;Sindija Smite;Elea Darras;Pavla Taborska;Dmitry Stakheev;Luca Vannucci;Jirina Bartunkova;Daniel Smrz - International journal of molecular sciences (2022)
  6. A digital platform for the design of patient-centric supply chains. - Niki Triantafyllou;Andrea Bernardi;Matthew Lakelin;Nilay Shah;Maria M Papathanasiou - Scientific reports (2022)
  7. Recent Advances in the Development of Anti-FLT3 CAR T-Cell Therapies for Treatment of AML. - Maya Graham Pedersen;Bjarne Kuno Møller;Rasmus O Bak - Biomedicines (2022)
  8. Activation of distinct antiviral T-cell immunity: A comparison of bi- and trispecific T-cell engager antibodies with a chimeric antigen receptor targeting HBV envelope proteins. - Bilge Debelec-Butuner;Oliver Quitt;Sophia Schreiber;Frank Momburg;Karin Wisskirchen;Ulrike Protzer - Frontiers in immunology (2022)
  9. DNA and mRNA Vaccines for Chronic Viral Infections and Cancer: Rationale, Mechanisms, and Progress. - Margaret A Liu - Cancers (2022)
  10. Joining Forces for Cancer Treatment: From "TCR versus CAR" to "TCR and CAR". - Karin Teppert;Xueting Wang;Kathleen Anders;César Evaristo;Dominik Lock;Annette Künkele - International journal of molecular sciences (2022)

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