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文献精选 > 高引权威"CAR-T疗法"文献

Chimeric antigen receptor (CAR) T therapies for the treatment of hematologic malignancies: clinical perspective and significance. ​

文献信息 ​

DOI10.1186/s40425-018-0460-5
PMID30514386
期刊Journal for immunotherapy of cancer
影响因子10.6
JCR 分区Q1
发表年份2018
被引次数133
关键词阿西卡替尼细胞疗法（Axicabtagene ciloleucel）, 嵌合抗原受体（Chimeric antigen receptor）, 白血病（Leukemia）, 淋巴瘤（Lymphoma）, 替佐普细胞疗法（Tisagenlecleucel）
文献类型Journal Article, Review
ISSN2051-1426
页码137
期号6(1)
作者Michael M Boyiadzis, Madhav V Dhodapkar, Renier J Brentjens, James N Kochenderfer, Sattva S Neelapu, Marcela V Maus, David L Porter, David G Maloney, Stephan A Grupp, Crystal L Mackall, Carl H June, Michael R Bishop

一句话小结 ​

嵌合抗原受体（CAR）T细胞疗法通过基因工程改造T细胞，已在血液恶性肿瘤治疗中取得显著成功，并获得FDA批准，促使该领域快速发展。本文综述了CAR T细胞疗法的重要性和临床考虑，为临床医生提供了关于这一革命性治疗的最新信息。

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阿西卡替尼细胞疗法（Axicabtagene ciloleucel） · 嵌合抗原受体（Chimeric antigen receptor） · 白血病（Leukemia） · 淋巴瘤（Lymphoma） · 替佐普细胞疗法（Tisagenlecleucel）

摘要 ​

嵌合抗原受体（CAR）T细胞疗法是一种经过基因工程改造的采纳性T细胞疗法，具有新的抗原特异性，已在治疗血液恶性肿瘤方面取得显著成功，导致最近有三项获得美国食品药品监督管理局（FDA）批准的案例。基于这些成功所带来的希望，该领域正在迅速发展，涵盖新的疾病适应症和CAR设计，同时对毒性和管理方案进行审查和优化。因此，本综述提供了对CAR T细胞疗法的重要性和临床考虑的专家观点，以便向临床医生提供关于这一革命性新治疗类别的及时信息。

英文摘要 ​

Chimeric Antigen Receptor (CAR) T cell therapies - adoptive T cell therapies that have been genetically engineered for a new antigen-specificity - have displayed significant success in treating patients with hematologic malignancies, leading to three recent US Food and Drug Administration approvals. Based on the promise generated from these successes, the field is rapidly evolving to include new disease indications and CAR designs, while simultaneously reviewing and optimizing toxicity and management protocols. As such, this review provides expert perspective on the significance and clinical considerations of CAR T cell therapies in order to provide timely information to clinicians about this revolutionary new therapeutic class.

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主要研究问题 ​

  1. CAR T 细胞疗法在不同类型的血液恶性肿瘤中的疗效和适应症有哪些具体差异？
  2. 在 CAR T 细胞疗法的临床应用中，患者的个体差异如何影响治疗效果？
  3. 除了血液恶性肿瘤，CAR T 细胞疗法是否有潜力应用于其他类型的癌症？如果有，具体是哪些？
  4. 当前 CAR T 细胞疗法在管理毒性方面有哪些最新的研究和实践进展？
  5. 在未来的 CAR T 细胞疗法研究中，有哪些新兴的设计或策略可能会提高疗效或降低副作用？

核心洞察 ​

研究背景和目的 ​

嵌合抗原受体（CAR）T细胞疗法是一种通过基因工程改造的采用性T细胞疗法，显示出在治疗血液恶性肿瘤方面的显著成功，已经获得了FDA的批准。本文综述了CAR T细胞疗法的临床意义、毒性管理和技术进展，以便为临床医生提供相关信息。

主要方法/材料/实验设计 ​

CAR T细胞疗法的主要步骤包括：

  1. 免疫细胞采集：通过大容量白细胞分离术从患者体内采集外周血单核细胞。
  2. 细胞工程：在良好生产规范（GMP）设施中，使用编码CAR的病毒载体对T细胞进行基因转导，生成CAR T细胞。
  3. 细胞扩增：转导后的T细胞在体外扩增，通常需要约3周的时间。
  4. 患者输注：将扩增后的CAR T细胞回输给患者。
Mermaid diagram

关键结果和发现 ​

  1. 疗效：CAR T细胞疗法在B细胞恶性肿瘤（如急性淋巴细胞白血病和弥漫性大B细胞淋巴瘤）中显示出高达82%的客观反应率。
  2. 毒性：主要毒性包括细胞因子释放综合征（CRS）和神经毒性（NTX），这些毒性在治疗后几天内出现，且与患者的疾病负担相关。
  3. FDA批准：截至2018年，已有两种CAR T疗法获得FDA批准，分别为tisagenlecleucel和axicabtagene ciloleucel。

主要结论/意义/创新性 ​

CAR T细胞疗法为治疗血液恶性肿瘤提供了新的希望，尤其是对那些传统疗法无效的患者。尽管取得了显著进展，但仍需进一步研究以优化疗法的安全性和有效性。

研究局限性和未来方向 ​

  1. 局限性：CAR T细胞疗法的适应症主要集中在血液恶性肿瘤，且毒性管理仍是一个挑战。
  2. 未来方向：未来研究将聚焦于扩大适应症（如固体肿瘤）、改进CAR设计（如多特异性CAR）以及提高疗法的耐受性和持久性。新一代CAR T细胞疗法（如IL-12分泌CAR T细胞）和全能性CAR T细胞的开发正在进行中，预期将进一步提升治疗效果。

研究局限性和未来方向 ​

局限性未来方向
主要集中于血液恶性肿瘤扩展至固体肿瘤
毒性管理仍具挑战改进CAR设计以提高耐受性
临床数据尚需更多验证开发新一代CAR T细胞

综上所述，CAR T细胞疗法在血液恶性肿瘤的治疗中展现出巨大潜力，尽管面临挑战，但其未来发展前景广阔。

参考文献 ​

  1. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. - Xiaoou Zhou;Gianpietro Dotti;Robert A Krance;Caridad A Martinez;Swati Naik;Rammurti T Kamble;April G Durett;Olga Dakhova;Barbara Savoldo;Antonio Di Stasi;David M Spencer;Yu-Feng Lin;Hao Liu;Bambi J Grilley;Adrian P Gee;Cliona M Rooney;Helen E Heslop;Malcolm K Brenner - Blood (2015)
  2. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. - James N Kochenderfer;Wyndham H Wilson;John E Janik;Mark E Dudley;Maryalice Stetler-Stevenson;Steven A Feldman;Irina Maric;Mark Raffeld;Debbie-Ann N Nathan;Brock J Lanier;Richard A Morgan;Steven A Rosenberg - Blood (2010)
  3. IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors in vivo. - Mythili Koneru;Terence J Purdon;David Spriggs;Susmith Koneru;Renier J Brentjens - Oncoimmunology (2015)
  4. Current concepts in the diagnosis and management of cytokine release syndrome. - Daniel W Lee;Rebecca Gardner;David L Porter;Chrystal U Louis;Nabil Ahmed;Michael Jensen;Stephan A Grupp;Crystal L Mackall - Blood (2014)
  5. Natural killer cell adoptive immunotherapy: Coming of age. - Letícia Baggio;Álvaro Macedo Laureano;Lucia Mariano da Rocha Silla;Dean Anthony Lee - Clinical immunology (Orlando, Fla.) (2017)
  6. Targeting B-cell maturation antigen in multiple myeloma. - Yu-Tzu Tai;Kenneth C Anderson - Immunotherapy (2015)
  7. Lymphoma Remissions Caused by Anti-CD19 Chimeric Antigen Receptor T Cells Are Associated With High Serum Interleukin-15 Levels. - James N Kochenderfer;Robert P T Somerville;Tangying Lu;Victoria Shi;Adrian Bot;John Rossi;Allen Xue;Stephanie L Goff;James C Yang;Richard M Sherry;Christopher A Klebanoff;Udai S Kammula;Marika Sherman;Arianne Perez;Constance M Yuan;Tatyana Feldman;Jonathan W Friedberg;Mark J Roschewski;Steven A Feldman;Lori McIntyre;Mary Ann Toomey;Steven A Rosenberg - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2017)
  8. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. - Robert O Carpenter;Moses O Evbuomwan;Stefania Pittaluga;Jeremy J Rose;Mark Raffeld;Shicheng Yang;Ronald E Gress;Frances T Hakim;James N Kochenderfer - Clinical cancer research : an official journal of the American Association for Cancer Research (2013)
  9. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. - Joseph A Fraietta;Simon F Lacey;Elena J Orlando;Iulian Pruteanu-Malinici;Mercy Gohil;Stefan Lundh;Alina C Boesteanu;Yan Wang;Roddy S O'Connor;Wei-Ting Hwang;Edward Pequignot;David E Ambrose;Changfeng Zhang;Nicholas Wilcox;Felipe Bedoya;Corin Dorfmeier;Fang Chen;Lifeng Tian;Harit Parakandi;Minnal Gupta;Regina M Young;F Brad Johnson;Irina Kulikovskaya;Li Liu;Jun Xu;Sadik H Kassim;Megan M Davis;Bruce L Levine;Noelle V Frey;Donald L Siegel;Alexander C Huang;E John Wherry;Hans Bitter;Jennifer L Brogdon;David L Porter;Carl H June;J Joseph Melenhorst - Nature medicine (2018)
  10. Long-Duration Complete Remissions of Diffuse Large B Cell Lymphoma after Anti-CD19 Chimeric Antigen Receptor T Cell Therapy. - James N Kochenderfer;Robert P T Somerville;Tangying Lu;James C Yang;Richard M Sherry;Steven A Feldman;Lori McIntyre;Adrian Bot;John Rossi;Norris Lam;Steven A Rosenberg - Molecular therapy : the journal of the American Society of Gene Therapy (2017)

引用本文的文献 ​

  1. Navigating the Fas lane to improved cellular therapy for cancer. - Madhav V Dhodapkar - The Journal of clinical investigation (2019)
  2. Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells. - Mohamed-Reda Benmebarek;Clara Helke Karches;Bruno Loureiro Cadilha;Stefanie Lesch;Stefan Endres;Sebastian Kobold - International journal of molecular sciences (2019)
  3. Arming T Cells with a gp100-Specific TCR and a CSPG4-Specific CAR Using Combined DNA- and RNA-Based Receptor Transfer. - Bianca Simon;Dennis C Harrer;Beatrice Schuler-Thurner;Gerold Schuler;Ugur Uslu - Cancers (2019)
  4. Overview of Targeted Drugs for Mature B-Cell Non-hodgkin Lymphomas. - Stefania Crisci;Raffaele Di Francia;Sara Mele;Pasquale Vitale;Giuseppina Ronga;Rosaria De Filippi;Massimiliano Berretta;Paola Rossi;Antonio Pinto - Frontiers in oncology (2019)
  5. Effects of interleukin-2 in immunostimulation and immunosuppression. - Jonathan G Pol;Pamela Caudana;Juliette Paillet;Eliane Piaggio;Guido Kroemer - The Journal of experimental medicine (2020)
  6. TraFo-CRISPR: Enhanced Genome Engineering by Transient Foamy Virus Vector-Mediated Delivery of CRISPR/Cas9 Components. - Fabian Lindel;Carolin R Dodt;Niklas Weidner;Monique Noll;Fabian Bergemann;Rayk Behrendt;Sarah Fischer;Josephine Dietrich;Marc Cartellieri;Martin V Hamann;Dirk Lindemann - Molecular therapy. Nucleic acids (2019)
  7. The Cross Talk between Cancer Stem Cells/Cancer Initiating Cells and Tumor Microenvironment: The Missing Piece of the Puzzle for the Efficient Targeting of these Cells with Immunotherapy. - Shilpa Ravindran;Saad Rasool;Cristina Maccalli - Cancer microenvironment : official journal of the International Cancer Microenvironment Society (2019)
  8. T Cell Reprogramming Against Cancer. - Samuel G Katz;Peter M Rabinovich - Methods in molecular biology (Clifton, N.J.) (2020)
  9. Molecular Imaging with Reporter Genes: Has Its Promise Been Delivered? - Inna Serganova;Ronald G Blasberg - Journal of nuclear medicine : official publication, Society of Nuclear Medicine (2019)
  10. IL-23 and PSMA-targeted duo-CAR T cells in Prostate Cancer Eradication in a preclinical model. - Dawei Wang;Yuan Shao;Xiang Zhang;Guoliang Lu;Boke Liu - Journal of translational medicine (2020)

... (123 更多 篇文献)

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