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CAR T therapies in multiple myeloma: unleashing the future. ​

文献信息 ​

DOI10.1038/s41417-024-00750-2
PMID38438559
期刊Cancer gene therapy
影响因子5.0
JCR 分区Q1
发表年份2024
被引次数62
关键词CAR T细胞疗法, 多发性骨髓瘤, 抗原靶向治疗, 临床试验, 治疗反应
文献类型Journal Article, Review
ISSN0929-1903
页码667-686
期号31(5)
作者Mohsen Sheykhhasan, Amirhossein Ahmadieh-Yazdi, Rosario Vicidomini, Naresh Poondla, Hamid Tanzadehpanah, Ashkan Dirbaziyan, Hanie Mahaki, Hamed Manoochehri, Naser Kalhor, Paola Dama

一句话小结 ​

本文探讨了CAR T细胞疗法在治疗多发性骨髓瘤中的应用，强调其作为一种新兴治疗手段的潜力，尤其是在对复发/难治性多发性骨髓瘤患者的治疗中。尽管存在一定的挑战和局限性，研究表明该疗法有望增强治疗效果并减少副作用，对癌症治疗领域具有重要意义。

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CAR T细胞疗法 · 多发性骨髓瘤 · 抗原靶向治疗 · 临床试验 · 治疗反应

摘要 ​

近年来，癌症治疗领域经历了显著的突破，彻底改变了癌症患者的护理格局。虽然手术、化疗和放疗等传统治疗手段早已存在，但一种名为CAR T细胞疗法的前沿治疗方法已成为治疗多发性骨髓瘤（MM）的重大变革者。这种新颖的治疗方法通过利用具有强大补体依赖性细胞毒作用的蛋白复合物或抗CD38抗体，补充了自体干细胞移植和免疫调节药物（如蛋白酶体抑制剂）等选项。尽管与这些治疗相关的挑战和障碍依然存在，但FDA最近批准的第二种多发性骨髓瘤CAR T细胞疗法给该领域带来了巨大的希望。目前的结果表明，这种疗法具有作为一种高效治疗解决方案的潜力。此外，目前正在进行的临床前和临床试验正在探索CAR T细胞在针对骨髓瘤细胞特定抗原方面的能力，为复发/难治性多发性骨髓瘤（RRMM）患者带来了希望。这些进展显示出基于CAR T细胞的药物或联合疗法在引发更强的治疗反应和减少副作用方面的潜力。在这一背景下，深入探讨CAR T细胞的历史和功能，同时认识到其局限性至关重要。通过理解这些挑战，我们可以制定战略并开发创新方法来克服这些障碍。本文旨在提供关于CAR T细胞在治疗多发性骨髓瘤中的应用的见解，揭示其潜力、局限性以及提高其疗效所采取的策略。

英文摘要 ​

In recent years, the field of cancer treatment has witnessed remarkable breakthroughs that have revolutionized the landscape of care for cancer patients. While traditional pillars such as surgery, chemotherapy, and radiation therapy have long been available, a cutting-edge therapeutic approach called CAR T-cell therapy has emerged as a game-changer in treating multiple myeloma (MM). This novel treatment method complements options like autologous stem cell transplants and immunomodulatory medications, such as proteasome inhibitors, by utilizing protein complexes or anti-CD38 antibodies with potent complement-dependent cytotoxic effects. Despite the challenges and obstacles associated with these treatments, the recent approval of the second FDA multiple myeloma CAR T-cell therapy has sparked immense promise in the field. Thus far, the results indicate its potential as a highly effective therapeutic solution. Moreover, ongoing preclinical and clinical trials are exploring the capabilities of CAR T-cells in targeting specific antigens on myeloma cells, offering hope for patients with relapsed/refractory MM (RRMM). These advancements have shown the potential for CAR T cell-based medicines or combination therapies to elicit greater treatment responses and minimize side effects. In this context, it is crucial to delve into the history and functions of CAR T-cells while acknowledging their limitations. We can strategize and develop innovative approaches to overcome these barriers by understanding their challenges. This article aims to provide insights into the application of CAR T-cells in treating MM, shedding light on their potential, limitations, and strategies employed to enhance their efficacy.

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主要研究问题 ​

  1. CAR T细胞疗法在多发性骨髓瘤中的应用前景如何与其他新兴疗法进行比较？
  2. 在CAR T细胞治疗的临床试验中，哪些特定抗原被认为是最有前景的靶点？
  3. 针对复发/难治性多发性骨髓瘤，CAR T细胞疗法的联合治疗策略有哪些潜在优势？
  4. CAR T细胞疗法的副作用管理有哪些最佳实践，以提高患者的治疗体验？
  5. 如何评估CAR T细胞疗法的长期疗效和患者生存率，特别是在多发性骨髓瘤患者中？

核心洞察 ​

研究背景和目的 ​

多发性骨髓瘤（MM）是第二常见的血液癌症，尽管传统治疗方法（如化疗和放疗）取得了一定进展，但MM仍然是一种难以治愈的疾病。近年来，嵌合抗原受体T细胞（CAR T细胞）疗法作为一种新兴的免疫治疗手段，在MM的治疗中展现出巨大的潜力。本文旨在探讨CAR T细胞疗法在MM治疗中的应用、潜在的限制及未来的发展方向。

主要方法/材料/实验设计 ​

研究采用了CAR T细胞疗法，通过对患者的T细胞进行基因工程改造，使其能够识别并攻击特定的肿瘤抗原。具体步骤如下：

Mermaid diagram
  • 患者外周血采集：通过白细胞分离技术提取T细胞。
  • T细胞分离与激活：对提取的T细胞进行激活以提高其增殖能力。
  • 转导CAR基因：使用病毒载体将CAR基因导入T细胞中，使其具备特异性识别肿瘤细胞的能力。
  • 扩增与冻存：扩增转导后的T细胞，并在适当条件下冻存以备使用。
  • 回输到患者体内：将经过改造和扩增的CAR T细胞回输给患者，进行肿瘤细胞攻击。

关键结果和发现 ​

  1. CAR T细胞疗法的有效性：针对B细胞成熟抗原（BCMA）的CAR T细胞（如idecabtagene vicleucel）在多发性骨髓瘤患者中显示出显著的治疗效果，部分患者达到了完全缓解（CR）。
  2. 不良反应：常见的副作用包括细胞因子释放综合症（CRS）和神经毒性。CRS发生率高达76%，而42%的患者经历了不同程度的神经毒性。
  3. 抗原逃逸：部分患者在治疗后出现抗原表达降低或缺失的现象，导致治疗效果减弱。

主要结论/意义/创新性 ​

CAR T细胞疗法为多发性骨髓瘤患者提供了一种新的治疗选择，尤其是对于复发和难治的病例。尽管目前的疗法在疗效和安全性上显示出良好的前景，但仍需克服抗原逃逸和副作用等挑战。未来的研究应聚焦于优化CAR设计、探索新的靶向抗原、以及改进患者的管理策略。

研究局限性和未来方向 ​

  • 局限性：目前的CAR T细胞疗法仍面临抗原逃逸、T细胞持久性不足及免疫抑制微环境等问题。
  • 未来方向：
    • 开发新一代CAR T细胞，结合多个靶抗原以提高疗效。
    • 引入生物安全开关技术，提升治疗的安全性。
    • 深入研究肿瘤微环境的影响，以优化CAR T细胞的功能和持久性。

通过持续的基础研究和临床试验，CAR T细胞疗法有望在多发性骨髓瘤的治疗中发挥更大的作用。

参考文献 ​

  1. The basic principles of chimeric antigen receptor design. - Michel Sadelain;Renier Brentjens;Isabelle Rivière - Cancer discovery (2013)
  2. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. - Jesus G Berdeja;Deepu Madduri;Saad Z Usmani;Andrzej Jakubowiak;Mounzer Agha;Adam D Cohen;A Keith Stewart;Parameswaran Hari;Myo Htut;Alexander Lesokhin;Abhinav Deol;Nikhil C Munshi;Elizabeth O'Donnell;David Avigan;Indrajeet Singh;Enrique Zudaire;Tzu-Min Yeh;Alicia J Allred;Yunsi Olyslager;Arnob Banerjee;Carolyn C Jackson;Jenna D Goldberg;Jordan M Schecter;William Deraedt;Sen Hong Zhuang;Jeffrey Infante;Dong Geng;Xiaoling Wu;Marlene J Carrasco-Alfonso;Muhammad Akram;Farah Hossain;Syed Rizvi;Frank Fan;Yi Lin;Thomas Martin;Sundar Jagannath - Lancet (London, England) (2021)
  3. Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma. - Holly Lee;Sungwoo Ahn;Ranjan Maity;Noemie Leblay;Bachisio Ziccheddu;Marietta Truger;Monika Chojnacka;Anthony Cirrincione;Michael Durante;Remi Tilmont;Elie Barakat;Mansour Poorebrahim;Sarthak Sinha;John McIntyre;Angela M Y Chan;Holly Wilson;Shari Kyman;Amrita Krishnan;Ola Landgren;Wencke Walter;Manja Meggendorfer;Claudia Haferlach;Torsten Haferlach;Hermann Einsele;Martin K Kortüm;Stefan Knop;Jean Baptiste Alberge;Andreas Rosenwald;Jonathan J Keats;Leo Rasche;Francesco Maura;Paola Neri;Nizar J Bahlis - Nature medicine (2023)
  4. A review on tumor heterogeneity and evolution in multiple myeloma: pathological, radiological, molecular genetics, and clinical integration. - Christian M Schürch;Leo Rasche;Leonie Frauenfeld;Niels Weinhold;Falko Fend - Virchows Archiv : an international journal of pathology (2020)
  5. The loss of neoantigens is an important reason for immune escape in multiple myeloma patients with high intratumor heterogeneity. - Yue Wang;Jiadai Xu;Tianwei Lan;Chi Zhou;Peng Liu - Cancer medicine (2023)
  6. Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma. - Gils Roex;Marijke Timmers;Kristien Wouters;Diana Campillo-Davo;Donovan Flumens;Wilfried Schroyens;Yiwei Chu;Zwi N Berneman;Eva Lion;Feifei Luo;Sébastien Anguille - Journal of hematology & oncology (2020)
  7. Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide. - Yawara Kawano;Shiho Fujiwara;Naoko Wada;Mikiko Izaki;Hiromichi Yuki;Yutaka Okuno;Kenichi Iyama;Hiroshi Yamasaki;Akira Sakai;Hiroaki Mitsuya;Hiroyuki Hata - International journal of oncology (2012)
  8. Chimeric antigen receptors for the adoptive T cell therapy of hematologic malignancies. - Marco L Davila;Diana C G Bouhassira;Jae H Park;Kevin J Curran;Eric L Smith;Hollie J Pegram;Renier Brentjens - International journal of hematology (2014)
  9. Clinical responses with T lymphocytes targeting malignancy-associated κ light chains. - Carlos A Ramos;Barbara Savoldo;Vicky Torrano;Brandon Ballard;Huimin Zhang;Olga Dakhova;Enli Liu;George Carrum;Rammurti T Kamble;Adrian P Gee;Zhuyong Mei;Meng-Fen Wu;Hao Liu;Bambi Grilley;Cliona M Rooney;Malcolm K Brenner;Helen E Heslop;Gianpietro Dotti - The Journal of clinical investigation (2016)
  10. FDA Approval Summary: Idecabtagene Vicleucel for Relapsed or Refractory Multiple Myeloma. - Poornima Sharma;Bindu Kanapuru;Bindu George;Xue Lin;Zhenzhen Xu;Wilson W Bryan;Richard Pazdur;Marc R Theoret - Clinical cancer research : an official journal of the American Association for Cancer Research (2022)

引用本文的文献 ​

  1. Role of Immune Cells and Immunotherapy in Multiple Myeloma. - Vijay Radhakrishnan;Upendarrao Golla;Avinash Kundadka Kudva - Life (Basel, Switzerland) (2024)
  2. Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill. - Paschalis Evangelidis;Nikolaos Evangelidis;Panagiotis Kalmoukos;Maria Kourti;Athanasios Tragiannidis;Eleni Gavriilaki - Current issues in molecular biology (2024)
  3. Clinician and administrator perspectives on outpatient administration of ciltacabtagene autoleucel in relapsed or refractory multiple myeloma. - Doris K Hansen;Binod Dhakal;Mehdi Hamadani;David Dingli;Tania Jain;Carol Ann Huff;Murali Janakiram;Yi-Hsuan Liu;Kevin C De Braganca;Nicole Lodowski;Jennifer Sander;Peter Okorozo;Lindsay McFarland;Matthew Perciavalle;Stephen Huo;Zaina P Qureshi;Krina K Patel - Frontiers in immunology (2024)
  4. The Interplay between the DNA Damage Response (DDR) Network and the Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Multiple Myeloma. - Panagiotis Malamos;Christina Papanikolaou;Maria Gavriatopoulou;Meletios A Dimopoulos;Evangelos Terpos;Vassilis L Souliotis - International journal of molecular sciences (2024)
  5. Pathways to therapy resistance: The sheltering effect of the bone marrow microenvironment to multiple myeloma cells. - Kuntal Bhowmick;Max von Suskil;Omar S Al-Odat;Weam Othman Elbezanti;Subash C Jonnalagadda;Tulin Budak-Alpdogan;Manoj K Pandey - Heliyon (2024)
  6. Review of CAR T-Cell Therapy in Multiple Myeloma: A Canadian Perspective. - Steven Chun-Min Shih;Sita Bhella - Current oncology (Toronto, Ont.) (2024)
  7. The next frontier in immunotherapy: potential and challenges of CAR-macrophages. - Jing Li;Ping Chen;Wenxue Ma - Experimental hematology & oncology (2024)
  8. Targeting B-cell maturation antigen for treatment and monitoring of relapsed/refractory multiple myeloma patients: a comprehensive review. - David Yashar;Bernard Regidor;Marissa-Skye Goldwater;Sean Bujarski;Ashley Del Dosso;James R Berenson - Therapeutic advances in hematology (2024)
  9. CAR T-cell therapy in cancer: Integrating nursing perspectives for enhanced patient care. - Ashna Gupta;Gunjan Dagar;Mohd Umar Rehmani;Chandra Prakash Prasad;Deepak Saini;Mayank Singh;Abhishek Shankar - Asia-Pacific journal of oncology nursing (2024)
  10. Galectin-9 - ligand axis: an emerging therapeutic target for multiple myeloma. - Rajib K Shil;Norhan B B Mohammed;Charles J Dimitroff - Frontiers in immunology (2024)

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