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文献精选 > 近年高分"CAR-T疗法"研究（IF≥30，近5年）

Chimeric antigen receptor T cell therapies for multiple myeloma. ​

文献信息 ​

DOI10.1186/s13045-019-0823-5
PMID31752943
期刊Journal of hematology & oncology
影响因子40.4
JCR 分区Q1
发表年份2019
被引次数20
关键词嵌合抗原受体, 免疫治疗, 多发性骨髓瘤, 肿瘤免疫学
文献类型Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN1756-8722
页码120
期号12(1)
作者Chao Wu, Lina Zhang, Qierra R Brockman, Fenghuang Zhan, Lijuan Chen

一句话小结 ​

多发性骨髓瘤（MM）作为一种常见的血液恶性肿瘤，尽管已有多种新药物，但仍缺乏治愈方案，尤其是对难治性/复发性MM的治疗需求迫切。本文总结了嵌合抗原受体（CAR）T细胞治疗在MM领域的最新进展，包括靶点、技术创新及初步结果，为未来的治疗发展提供了重要的参考。

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嵌合抗原受体 · 免疫治疗 · 多发性骨髓瘤 · 肿瘤免疫学

摘要 ​

多发性骨髓瘤（MM）是第二常见的血液恶性肿瘤，尽管已经出现了许多新药物，如蛋白酶体抑制剂（PIs）、免疫调节剂（IMiDs）和单克隆抗体，但仍然没有治愈的方法。目前对于难治性/复发性MM的治疗需求亟待满足。近年来，嵌合抗原受体（CAR）改造的T细胞治疗在MM的临床前和临床研究中显示出良好的疗效。此外，CAR-T细胞治疗的毒性是可管理的。本文总结了CAR-T治疗在MM领域的最新进展，重点关注有前景的靶点、新技术和新研究领域。此外，还提供了对抗原选择的全面概述，以及CAR-T治疗开发的初步结果和未来方向。

英文摘要 ​

Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable despite the advent of numerous new drugs such as proteasome inhibitors (PIs), immunomodulatory agents (IMiDs), and monoclonal antibodies. There is an unmet need to develop novel therapies for refractory/relapsed MM. In the past few years, chimeric antigen receptor (CAR)-modified T cell therapy for MM has shown promising efficacy in preclinical and clinical studies. Furthermore, the toxicities of CAR-T cell therapy are manageable. This article summarizes recent developments of CAR-T therapy in MM, focusing on promising targets, new technologies, and new research areas. Additionally, a comprehensive overview of antigen selection is presented along with preliminary results and future directions of CAR-T therapy development.

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主要研究问题 ​

  1. 在CAR-T细胞治疗中，针对多发性骨髓瘤的主要靶点有哪些，如何选择这些靶点？
  2. CAR-T细胞治疗的临床试验结果如何，与传统治疗方法相比，疗效有何不同？
  3. 在CAR-T细胞治疗中，如何评估和管理潜在的毒性反应？
  4. 目前在多发性骨髓瘤中，CAR-T细胞疗法的最新技术进展有哪些，未来的研究方向是什么？
  5. 除了CAR-T细胞治疗，还有哪些新兴的免疫治疗方法可以应用于多发性骨髓瘤的治疗？

核心洞察 ​

研究背景和目的 ​

多发性骨髓瘤（MM）是第二常见的血液恶性肿瘤，尽管有多种新药物（如蛋白酶体抑制剂、免疫调节剂和单克隆抗体）问世，但仍然难以治愈。MM患者常常在治疗后复发并对后续治疗产生耐药性。因此，开发新型治疗方法，尤其是针对难治性和复发性MM的治疗策略，显得尤为重要。近年来，嵌合抗原受体（CAR）T细胞治疗在MM的预临床和临床研究中显示出良好的疗效。

主要方法/材料/实验设计 ​

本研究回顾了CAR-T治疗在MM中的最新进展，重点讨论了靶点选择、新技术及研究领域。CAR-T治疗的关键在于靶点选择，适合的靶点应专门表达于MM细胞，以避免“靶向/非肿瘤”毒性。主要靶点包括B细胞成熟抗原（BCMA）、CD19、CD138等。

Mermaid diagram

关键结果和发现 ​

  1. BCMA靶向CAR-T治疗：BCMA是MM细胞特异性表达的靶点，相关临床试验显示高达81%的总反应率（ORR）。然而，高剂量治疗中出现了显著的细胞因子释放综合症（CRS）。
  2. 其他靶点：如CD19和CD138等靶点也在研究中显示出一定的疗效，但CD19在MM细胞中的表达相对较少。
  3. 组合疗法：结合CD19和BCMA靶向的CAR-T细胞显示出更好的反应率，表明多靶点治疗的潜力。

主要结论/意义/创新性 ​

CAR-T治疗在MM的应用展现出良好的疗效和相对可控的安全性，特别是针对BCMA的CAR-T疗法显示出显著的临床效果。未来的研究应聚焦于优化靶点选择、改进CAR结构及治疗方案，以提高治疗的持久性和降低毒性。此外，CAR-T治疗与其他免疫疗法的联合使用也显示出增强的治疗效果。

研究局限性和未来方向 ​

尽管CAR-T治疗展现出良好的前景，但仍面临以下局限性：

  • 毒性管理：CRS及其他相关副作用需要有效管理，当前使用的治疗手段（如IL-6拮抗剂）效果有限。
  • 靶点选择：需要进一步探索MM细胞的表面抗原，以识别新的治疗靶点。
  • 耐药性：如何克服治疗后的耐药性是未来研究的重要方向。

未来的研究应集中于开发更为安全有效的CAR-T治疗方案，探索新靶点，以及与其他疗法的联合应用。

参考文献 ​

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  2. Preclinical characterization of SGN-70, a humanized antibody directed against CD70. - Julie A McEarchern;Leia M Smith;Charlotte F McDonagh;Kerry Klussman;Kristine A Gordon;Carol A Morris-Tilden;Steven Duniho;Maureen Ryan;Tamar E Boursalian;Paul J Carter;Iqbal S Grewal;Che-Leung Law - Clinical cancer research : an official journal of the American Association for Cancer Research (2008)
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  6. Anti-BCMA CAR-T cells for treatment of plasma cell dyscrasia: case report on POEMS syndrome and multiple myeloma. - Jinhuan Xu;Qiuxiang Wang;Hao Xu;Chaojiang Gu;Lijun Jiang;Jue Wang;Di Wang;Bin Xu;Xia Mao;Jin Wang;Zhiqiong Wang;Yi Xiao;Yicheng Zhang;Chunrui Li;Jianfeng Zhou - Journal of hematology & oncology (2018)
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  9. Heparanase-induced shedding of syndecan-1/CD138 in myeloma and endothelial cells activates VEGFR2 and an invasive phenotype: prevention by novel synstatins. - O Jung;V Trapp-Stamborski;A Purushothaman;H Jin;H Wang;R D Sanderson;A C Rapraeger - Oncogenesis (2016)
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引用本文的文献 ​

  1. Next-generation immuno-oncology agents: current momentum shifts in cancer immunotherapy. - Chongxian Pan;Hongtao Liu;Elizabeth Robins;Wenru Song;Delong Liu;Zihai Li;Lei Zheng - Journal of hematology & oncology (2020)
  2. Deregulation of Adaptive T Cell Immunity in Multiple Myeloma: Insights Into Mechanisms and Therapeutic Opportunities. - Noémie Leblay;Ranjan Maity;Fajer Hasan;Paola Neri - Frontiers in oncology (2020)
  3. Characterization of novel dual tandem CD19/BCMA chimeric antigen receptor T cells to potentially treat multiple myeloma. - Liqing Kang;Jian Zhang;Minghao Li;Nan Xu;Wei Qi;Jingwen Tan;Xiaoyan Lou;Zhou Yu;Juanjuan Sun;Zhenkun Wang;Chengcheng Fu;Xiaowen Tang;Haiping Dai;Jia Chen;Depei Wu;Lei Yu - Biomarker research (2020)
  4. Overcoming Chimeric Antigen Receptor (CAR) Modified T-Cell Therapy Limitations in Multiple Myeloma. - Estefanía García-Guerrero;Belén Sierro-Martínez;Jose Antonio Pérez-Simón - Frontiers in immunology (2020)
  5. BCMA-targeted immunotherapy for multiple myeloma. - Bo Yu;Tianbo Jiang;Delong Liu - Journal of hematology & oncology (2020)
  6. Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in A Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease. - Sébastien Gouard;Catherine Maurel;Séverine Marionneau-Lambot;Delphine Dansette;Clément Bailly;François Guérard;Nicolas Chouin;Ferid Haddad;Cyril Alliot;Joëlle Gaschet;Romain Eychenne;Françoise Kraeber-Bodéré;Michel Chérel - Cancers (2020)
  7. Clinical implication of cellular vaccine in glioma: current advances and future prospects. - Yuanliang Yan;Shuangshuang Zeng;Zhicheng Gong;Zhijie Xu - Journal of experimental & clinical cancer research : CR (2020)
  8. 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)
  9. Chimeric antigen receptor- and natural killer cell receptor-engineered innate killer cells in cancer immunotherapy. - Cai Zhang;Yuan Hu;Weihua Xiao;Zhigang Tian - Cellular & molecular immunology (2021)
  10. Novel strategies for immuno-oncology breakthroughs with cell therapy. - Hongtao Liu;Chongxian Pan;Wenru Song;Delong Liu;Zihai Li;Lei Zheng - Biomarker research (2021)

... (10 更多 篇文献)

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