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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2023, Vol. 43 Issue (6): 43-53    DOI: 10.13523/j.cb.2302031
综述     
CAR-T在血液类恶性肿瘤中的研究进展*
董蒨蒨,李玉淼**()
山西高等创新研究院 太原 030032
Research Advances in CAR-T Cell Immunotherapy in Hematologic Malignancies
DONG Qian-qian,LI Yu-miao**()
Shanxi Academy of Advanced Research and Innovation, Taiyuan 030032, China
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摘要：

近年来,我国血液系统恶性肿瘤的发病率逐年上升。目前血液系统恶性肿瘤的治疗以化疗、骨髓移植为主,化疗副作用大且损伤患者的正常组织器官,而骨髓移植面临着配型、排异反应等一系列问题。嵌合抗原受体T细胞免疫治疗,即CAR-T,近年来在恶性肿瘤治疗中取得了较大的突破和进展,尤其在血液类肿瘤的临床治疗中获得很大成就。但CAR-T也面临缺乏特异性靶点、肿瘤微环境抑制及实体瘤浸润效果不佳等问题。就CAR-T 细胞的原理、发展历史、目前的研究进展及存在问题作简单介绍,同时对CAR-T在血液类恶性肿瘤临床应用现状及前景进行详细总结和讨论,最后对CAR-T在实体瘤中的研究困境及方向进行概述、探讨,为后续相关研究提供参考依据。
关键词： CAR-T细胞;  血液肿瘤;  淋巴肿瘤;  细胞免疫治疗;  肿瘤治疗    
Abstract:

In recent years, the incidence rate of hematological malignancies has increased year by year in China. At present, chemotherapy and bone marrow transplantation are the main methods for treating hematological malignancies. Chemotherapy has significant side effects and damages the normal tissues and organs of patients, and bone marrow transplantation faces a series of problems such as typing and rejection reactions. Chimeric antigen receptor modifies T cells, namely CAR T cell immunotherapy, which has made great breakthrough and progress in the treatment of malignant tumors in recent years, especially in the clinical treatment of hematological tumors. However, CAR-T cell immunotherapy also faces the problems of a lack of specific targets, inhibition of tumor microenvironment and poor effect of solid tumor invasion. This article briefly introduces the principle, development history, current research progress and existing problems of CAR-T cells. Meanwhile, the clinical application status and prospect of CAR-T cells in hematologic malignancies are summarized and discussed in detail. Finally, we summarize and discuss the research difficulties and directions of CAR-T therapy in solid tumors, so as to provide a reference for subsequent related studies.
Key words: CAR-T cell    Hematological tumors    Lymphatic tumors    Cell immunotherapy    Tumor treatment
收稿日期: 2023-02-17 出版日期: 2023-07-04
ZTFLH:  Q291  
基金资助: * 山西转型综合改革示范区科技创新项目(YDZJSX2021C037)
通讯作者: **电子信箱:liyumiao29@163.com   
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董蒨蒨
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引用本文:

董蒨蒨, 李玉淼. CAR-T在血液类恶性肿瘤中的研究进展*[J]. 中国生物工程杂志, 2023, 43(6): 43-53.

DONG Qian-qian, LI Yu-miao. Research Advances in CAR-T Cell Immunotherapy in Hematologic Malignancies. China Biotechnology, 2023, 43(6): 43-53.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2302031    或    https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I6/43

图1  CAR-T第一信号、第二信号通路图
图2  CAR-T细胞生产及过程质量控制流程图
图3  CAR结构示意图
图4  历代CAR结构发展、演变示意图
图5  血液类恶性肿瘤分类
机构/研发人员 适应证 靶点 患者数量 疗效 参考文献
Maude等 复发/难治急性B淋巴细胞白血病 CD19 30 90%患者达到完全缓解,6个月的无事件生存率为67%,总生存率为78% [19]
北京博仁医院童春容团队 复发/难治急性B淋巴细胞白血病 CD19 51 90%患者达到完全缓解,联合CD22 CAR-T治疗,缓解率可再达71%,总体治愈率超过60% [20]
华中科技大学同济医院周剑峰团队 复发/难治急性B淋巴细胞白血病 CD19/
CD22		 42 完全缓解率为90.5%,部分缓解率为7.1%;6个月无事件生存率为60.5%,总生存率为80.0%;12个月无事件生存率为41.2%,总生存率为57.1% [21]
北京博仁医院童春容、刘双又团队 复发/难治急性B淋巴细胞白血病 CD19 19 13名患者完全缓解,完全缓解率达68% [22]
Munshi等 复发/难治性骨髓瘤 BCMA 128 94名患者(73%)对于治疗有反应,其中42名(33%)患者获得了完全缓解。在完全缓解的42名患者中有33名(79%)患者处于MRD阴性状态,中位无进展生存期为8.8个月。 [23]
传奇生物和杨森 复发/难治性骨髓瘤 BCMA 97 97名接受治疗的患者ORR高达94.8%。生存数据方面,6个月无事件生存率为87.4%,总生存率为93.8%。 [24]
徐州医科大学血液病研究所徐开林、李振宇团队 复发/难治性骨髓瘤 GPRC5D 33 总治愈率为91%,11名(33%)患者为严格意义上的完全缓解,10名(30%)患者得到完全缓解,4名(12%)患者得到非常好的部分缓解,5名(15%)患者得到部分缓解。 [25]
徐州医科大学血液病研究所徐开林团队 复发/难治性骨髓瘤 BCMA/
CD19		 69 总有效率为92%(57/62),37名患者(60%)得到完全缓解,77%(43/56)的患者处于MRD阴性状态,中位无进展生存期为18.3个月。 [26]
宾夕法尼亚大学Porter团队 复发或难治慢性淋巴细胞白血病 CD19 14 14例患者中4例(29%)获得完全缓解,4例为部分缓解(29%),所有患者18个月总生存率为71%,无进展生存率为28.6% [27]
解放军总医院韩为东团队 弥散大B细胞性淋巴瘤/惰性B细胞恶性肿瘤 CD20 11 6例(55%)获得完全缓解,3例(27%)获得部分缓解,2例(18%)疾病稳定,中位无进展生存期大于6个月 [28]
表1  CAR-T在血液类恶性肿瘤中的临床应用
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