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Barriers to Chimeric Antigen Receptor T-Cell (CAR-T) Therapies in Clinical Practice. ​

文献信息 ​

DOI10.1007/s40290-022-00428-w
PMID35672571
期刊Pharmaceutical medicine
影响因子4.5
JCR 分区Q1
发表年份2022
被引次数47
关键词嵌合抗原受体T细胞疗法, 癌症治疗, 临床障碍, 免疫反应, 制造限制
文献类型Journal Article, Review
ISSN1178-2595
页码163-171
期号36(3)
作者Ajeet Gajra, Abigail Zalenski, Aishwarya Sannareddy, Yolaine Jeune-Smith, Kandice Kapinos, Ankit Kansagra

一句话小结 ​

嵌合抗原受体T细胞（CAR-T）治疗是一种创新的癌症免疫治疗方法，已在多种复发性血液恶性肿瘤中取得积极临床结果，但其广泛应用仍面临物流、生产、毒性和经济等多方面的挑战。本文探讨了克服这些障碍的潜在解决方案，以推动CAR-T治疗的普及和可及性，具有重要的临床意义。

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嵌合抗原受体T细胞疗法 · 癌症治疗 · 临床障碍 · 免疫反应 · 制造限制

摘要 ​

嵌合抗原受体T细胞（CAR-T）治疗是一种革命性的癌症治疗方式，患者自身的T细胞被收集并在体外进行基因工程改造，以表达嵌合抗原受体（CAR）。这些经过重新编程的CAR-T细胞在重新输注回患者体内后，能够刺激针对表达抗原的恶性细胞的T细胞介导的免疫反应，从而导致细胞死亡。CAR-T药物在关键临床试验中的初步结果令人鼓舞，已在多种复发性血液恶性肿瘤中获得多项批准，包括急性淋巴细胞白血病（ALL）、弥漫性大B细胞淋巴瘤（DLBCL）、披衣淋巴瘤、滤泡性淋巴瘤，以及最近的多发性骨髓瘤。然而，自初始试验和美国食品药品监督管理局批准以来，该疗法的广泛应用面临重大障碍。CAR-T治疗的使用障碍包括复杂的物流、生产限制、毒性问题和经济负担。本文综述了克服这些障碍的潜在解决方案，以使这一改变生活的治疗方法能够广泛可及。

英文摘要 ​

Chimeric antigen receptor T-cell (CAR-T) therapy is a revolutionary cancer treatment modality where a patient's own T cells are collected and engineered ex vivo to express a chimeric antigen receptor (CAR). These reprogrammed CAR-T cells, when reinfused into the same patient, stimulate a T-cell mediated immune response against the antigen-expressing malignant cells leading to cell death. The initial results from pivotal clinical trials of CAR-T agents have been promising, leading to multiple approvals in various hematologic malignancies in the relapsed setting, including acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, follicular lymphoma, and, more recently, multiple myeloma. However, since the initial trials and US Food and Drug Administration approvals, there have been significant barriers to the widespread use of this therapy. The barriers to the use of CAR-T therapy include complex logistics, manufacturing limitations, toxicity concerns, and financial burden. This review discusses potential solutions to overcome these barriers in order to make this life-changing therapy widely accessible.

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主要研究问题 ​

  1. CAR-T疗法在不同类型癌症中的适用性如何，是否存在特定癌症对该疗法反应较差的情况？
  2. 除了现有的制造限制外，是否有其他技术进步可以提高CAR-T细胞的生产效率和质量？
  3. 针对CAR-T疗法的毒性问题，目前有哪些管理策略或预防措施被提出或应用？
  4. 在不同国家和地区，CAR-T疗法的费用结构是否存在显著差异，这对患者的可及性有何影响？
  5. 有哪些正在进行的研究或临床试验旨在解决CAR-T疗法在临床应用中的障碍？

核心洞察 ​

研究背景和目的 ​

嵌合抗原受体T细胞（CAR-T）疗法是一种革命性的癌症治疗方法，通过对患者自身T细胞进行基因工程改造，使其能够识别并攻击癌细胞。自2017年首次获得FDA批准以来，CAR-T疗法在多种血液恶性肿瘤中显示出良好的临床效果。然而，其广泛应用面临着诸多障碍，包括复杂的物流、制造限制、毒性问题及经济负担。本研究旨在探讨这些障碍，并提出潜在的解决方案，以促进CAR-T疗法的普及。

主要方法/材料/实验设计 ​

本研究采用文献综述的方法，分析CAR-T疗法的实施障碍和解决方案，主要分为以下几个方面：

  1. 患者适应症：研究临床试验与真实世界患者的适应症差异。
  2. 治疗中心和交付模式：探讨将CAR-T疗法从大型学术中心转移到社区医院的可能性。
  3. 授权流程：分析保险公司授权流程的复杂性。
  4. 制造复杂性：讨论CAR-T细胞从采集到应用的“静脉到静脉”时间的影响。
  5. 临床结果：评估CAR-T疗法的有效性和毒性。

以下是技术路线的流程图：

Mermaid diagram

关键结果和发现 ​

  1. 患者适应症：真实世界研究表明，许多符合条件的患者因临床试验的严格标准而被排除，但实际治疗效果相似。
  2. 治疗中心：建议将CAR-T疗法转移到社区医院进行，需对医务人员进行额外培训以确保安全性。
  3. 授权流程：保险公司授权的延迟严重影响了患者接受治疗的时机，需优化流程。
  4. 制造复杂性：CAR-T细胞的制造过程复杂且耗时，开发异体CAR-T细胞可减少患者等待时间。
  5. 临床结果：尽管CAR-T疗法的有效性显著，但毒性反应如细胞因子释放综合症（CRS）和神经毒性仍需重视。

主要结论/意义/创新性 ​

CAR-T疗法具有巨大的潜力，但其广泛应用受限于多种障碍。通过优化患者筛选、改善治疗中心的分布、简化授权流程及提高制造效率，可以显著提升CAR-T疗法的可及性和有效性。未来的研究应集中在新型CAR-T产品的开发和患者管理策略的改进上，以实现更好的治疗效果。

研究局限性和未来方向 ​

本研究主要基于文献综述，缺乏大规模临床试验数据的直接支持。未来的研究应：

  • 进行大规模的前瞻性研究，以验证真实世界数据的有效性。
  • 探索更安全的CAR-T细胞设计，减少毒性反应。
  • 评估异体CAR-T疗法的临床应用及其经济性。

总之，尽管CAR-T疗法面临诸多挑战，但通过持续的创新和改进，有望使其成为更广泛适用的癌症治疗选择。

参考文献 ​

  1. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. - Shannon L Maude;Theodore W Laetsch;Jochen Buechner;Susana Rives;Michael Boyer;Henrique Bittencourt;Peter Bader;Michael R Verneris;Heather E Stefanski;Gary D Myers;Muna Qayed;Barbara De Moerloose;Hidefumi Hiramatsu;Krysta Schlis;Kara L Davis;Paul L Martin;Eneida R Nemecek;Gregory A Yanik;Christina Peters;Andre Baruchel;Nicolas Boissel;Francoise Mechinaud;Adriana Balduzzi;Joerg Krueger;Carl H June;Bruce L Levine;Patricia Wood;Tetiana Taran;Mimi Leung;Karen T Mueller;Yiyun Zhang;Kapildeb Sen;David Lebwohl;Michael A Pulsipher;Stephan A Grupp - The New England journal of medicine (2018)
  2. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. - Sattva S Neelapu;Frederick L Locke;Nancy L Bartlett;Lazaros J Lekakis;David B Miklos;Caron A Jacobson;Ira Braunschweig;Olalekan O Oluwole;Tanya Siddiqi;Yi Lin;John M Timmerman;Patrick J Stiff;Jonathan W Friedberg;Ian W Flinn;Andre Goy;Brian T Hill;Mitchell R Smith;Abhinav Deol;Umar Farooq;Peter McSweeney;Javier Munoz;Irit Avivi;Januario E Castro;Jason R Westin;Julio C Chavez;Armin Ghobadi;Krishna V Komanduri;Ronald Levy;Eric D Jacobsen;Thomas E Witzig;Patrick Reagan;Adrian Bot;John Rossi;Lynn Navale;Yizhou Jiang;Jeff Aycock;Meg Elias;David Chang;Jeff Wiezorek;William Y Go - The New England journal of medicine (2017)
  3. CAR-T cells: Early successes in blood cancer and challenges in solid tumors. - Hassan Dana;Ghanbar Mahmoodi Chalbatani;Seyed Amir Jalali;Hamid Reza Mirzaei;Stephan A Grupp;Eloah Rabello Suarez;Catarina Rapôso;Thomas J Webster - Acta pharmaceutica Sinica. B (2021)
  4. Should criteria for inclusion in cancer clinical trials be expanded? - David E Gerber;Sandi L Pruitt;Ethan A Halm - Journal of comparative effectiveness research (2015)
  5. Real-World Experiences of CAR T-Cell Therapy for Large B-Cell Lymphoma: How Similar Are They to the Prospective Studies? - Kevin Tang;Loretta J Nastoupil - Journal of immunotherapy and precision oncology (2021)
  6. Economic Evaluation of Chimeric Antigen Receptor T-Cell Therapy by Site of Care Among Patients With Relapsed or Refractory Large B-Cell Lymphoma. - Gary H Lyman;Andy Nguyen;Sophie Snyder;Matthew Gitlin;Karen C Chung - JAMA network open (2020)
  7. Perspectives on outpatient administration of CAR-T cell therapy in aggressive B-cell lymphoma and acute lymphoblastic leukemia. - G Doug Myers;Michael R Verneris;Andre Goy;Richard T Maziarz - Journal for immunotherapy of cancer (2021)
  8. Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. - Tania Jain;Merav Bar;Ankit J Kansagra;Elise A Chong;Shahrukh K Hashmi;Sattva S Neelapu;Michael Byrne;Elad Jacoby;Aleksandr Lazaryan;Caron A Jacobson;Stephen M Ansell;Farrukh T Awan;Linda Burns;Veronika Bachanova;Catherine M Bollard;Paul A Carpenter;John F DiPersio;Mehdi Hamadani;Helen E Heslop;Joshua A Hill;Krishna V Komanduri;Craig A Kovitz;Hillard M Lazarus;Justin M Serrette;Mohamad Mohty;David Miklos;Arnon Nagler;Steven Z Pavletic;Bipin N Savani;Stephen J Schuster;Mohamed A Kharfan-Dabaja;Miguel-Angel Perales;Yi Lin - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (2019)
  9. Clinical Utilization of Chimeric Antigen Receptor T Cells in B Cell Acute Lymphoblastic Leukemia: An Expert Opinion from the European Society for Blood and Marrow Transplantation and the American Society for Blood and Marrow Transplantation. - Ankit J Kansagra;Noelle V Frey;Merav Bar;Theodore W Laetsch;Paul A Carpenter;Bipin N Savani;Helen E Heslop;Catherine M Bollard;Krishna V Komanduri;Dennis A Gastineau;Christian Chabannon;Miguel A Perales;Michael Hudecek;Mahmoud Aljurf;Leslie Andritsos;John A Barrett;Veronika Bachanova;Chiara Bonini;Armin Ghobadi;Saar I Gill;Joshua Hill;Saad Kenderian;Partow Kebriaei;Arnon Nagler;David Maloney;Hien D Liu;Nirali N Shah;Mohamed A Kharfan-Dabaja;Elizabeth J Shpall;Ghulam J Mufti;Laura Johnston;Elad Jacoby;Ali Bazarbachi;John F DiPersio;Steven Z Pavletic;David L Porter;Stephan A Grupp;Michel Sadelain;Mark R Litzow;Mohamad Mohty;Shahrukh K Hashmi - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (2019)
  10. '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)

引用本文的文献 ​

  1. Construction of a cuproptosis-related lncRNA signature for predicting prognosis and immune landscape in osteosarcoma patients. - Shumin Ni;Jinjiong Hong;Weilong Li;Meng Ye;Jinyun Li - Cancer medicine (2023)
  2. Tackling Mantle Cell Lymphoma in Europe. - Denis Horgan;Jan Walewski;Igor Aurer;Carlo Visco;Eva Giné;Bogdan Fetica;Mats Jerkeman;Marta Kozaric;Maria Gomes da Silva;Martin Dreyling - Healthcare (Basel, Switzerland) (2022)
  3. Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: Results from a comprehensive cancer center. - Sérgio Chacim;Teresa Monjardino;José Luís Cunha;Pedro Medeiros;Patrícia Redondo;Maria José Bento;José Mário Mariz - PloS one (2022)
  4. Innovation in BCMA CAR-T therapy: Building beyond the Model T. - Rahul Banerjee;Sarah S Lee;Andrew J Cowan - Frontiers in oncology (2022)
  5. International oncology drug approvals for multiregional or single-country clinical trials: A systematic review. - Min Zhang;Igho Onakpoya;Katrin Rupalla - Frontiers in medicine (2022)
  6. FDG-PET/CT in the Monitoring of Lymphoma Immunotherapy Response: Current Status and Future Prospects. - Akram Al-Ibraheem;Ahmed Saad Abdlkadir;Malik E Juweid;Kamal Al-Rabi;Mohammad Ma'koseh;Hikmat Abdel-Razeq;Asem Mansour - Cancers (2023)
  7. Recent advances in treatment of nodal and gastrointestinal follicular lymphoma. - Takuya Watanabe - World journal of gastroenterology (2023)
  8. How can Cytokine-induced killer cells overcome CAR-T cell limits. - Elisa Cappuzzello;Emilia Vigolo;Giulia D'Accardio;Giuseppe Astori;Antonio Rosato;Roberta Sommaggio - Frontiers in immunology (2023)
  9. Bringing CAR T cell therapy trials to underserved populations. - Hoda Badr;Rayne Rouce;Michael E Scheurer;Premal Lulla;Martha Mims;Pavan Reddy - Cancer cell (2023)
  10. Adoptive NK Cell Therapy - a Beacon of Hope in Multiple Myeloma Treatment. - Son Hai Vu;Ha Hong Pham;Thao Thi Phuong Pham;Thanh Thien Le;Manh-Cuong Vo;Sung-Hoon Jung;Je-Jung Lee;Xuan-Hung Nguyen - Frontiers in oncology (2023)

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