论著
ENGLISH ABSTRACT
B系肿瘤患者CAR19 T 细胞治疗后体内T细胞增殖的动力学特征
戴兰
梅仁
沈文红
朱子玲
蔡梦洁
平娜娜
钱崇升
何林燕
白霞
朱明清
作者及单位信息
·
DOI: 10.3760/cma.j.cn114452-20240730-00417
Kinetic characteristics of T cell expansion in patients with B tumor after CAR19 T cell therapy
Dai Lan
Mei Ren
Shen Wenhong
Zhu Ziling
Cai Mengjie
Ping Na′na
Qian Chongsheng
He Linyan
Bai Xia
Zhu Mingqing
Authors Info & Affiliations
Dai Lan
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou215006, China
Mei Ren
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou215006, China
Shen Wenhong
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou215006, China
Zhu Ziling
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou215006, China
Cai Mengjie
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou215006, China
Ping Na′na
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou215006, China
Qian Chongsheng
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou215006, China
He Linyan
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou215006, China
Bai Xia
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou215006, China
Zhu Mingqing
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou215006, China
·
DOI: 10.3760/cma.j.cn114452-20240730-00417
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摘要

目的观察CAR19 T细胞治疗B系肿瘤中,患者体内 T细胞的增殖动力学。

方法观察性研究。运用流式细胞术,对2021年11月1日至2023年12月31日在苏州大学附属第一医院接受CAR19 T细胞治疗的52例B 系肿瘤患者(包括12例B-ALL和40例NHL),治疗前后的CAR19+和CAR19-T细胞扩增水平及亚群的变化进行监测。并根据B系肿瘤治疗指南中的 疗效评估标准,将患者分为完全缓解组和未完全缓解组,采用 t检验或非参数秩和检验比较两组CAR19+和CAR19-T细胞各亚群差异。

结果患者CAR19+T细胞扩增峰值时,完全缓解组和未获得完全缓解组CAR19+T细胞中各亚群均无统计学差异;患者体内的CAR19-T细胞6个月后CD3+/CD4+/CD8-比例仍低于治疗前水平(48.0+27.2比63.1+19.7,<0.01)其中的亚群CD197+CD45RA+,CD197-CD45RA-比例恢复至治疗前水平,而CD197-CD45RA+比例低于治疗前水平(4.2+3.0比21.1+15.6,<0.01);CD3+/CD4-/CD8+比例6个月后恢复至治疗前水平,其中的亚群CD197-CD45RA-的比例恢复至治疗前水平,而CD197+CD45RA+(16.6+8.7比35.1+30.1,<0.01),CD197+CD45RA-(18.7+9.1比25.8+19.1,<0.01)比例仍低于治疗前水平。

结论CAR19 T细胞治疗后,不同疗效患者CAR19+T细胞各亚群比例无差异。治疗后体内CAR19-CD3+CD4-CD8+细胞比例要早于CD3+CD4+CD8-恢复,且两者各亚群的变化存在不同。此治疗方案对体内的CAR19-T细胞亚群的影响很大,且它的重建需要较长时间。

急性淋巴细胞白血病;淋巴瘤;免疫细胞治疗;T淋巴细胞
ABSTRACT

ObjectiveTo investigate the proliferation kinetics of T cells in patients with B-cell hematologic malignancies who received CAR19 T cell therapy.

MethodsObservational study. Flow cytometry was used to monitor the levels of CAR19+and CAR19-T cell expansion and the dynamic changes of T lymphocyte subsets before and after CAR19 T cell therapy. The 52 patients with B-cell hematologic malignancies (including 12 B-ALL and 40 NHL) who received CAR19 T cell therapy in the First Affiliated Hospital of Soochow University from November 2021 to December 2023 were recruited in this study. Patients were divided into complete response group and incomplete response group according to the efficacy evaluation criteria in the treatment guidelines for B-cell hematologic malignancies. T test or non-parametric rank sum test were used to compare the differences of CAR19+and CAR19-T cell subsets between the two groups.

ResultsAt the peak of CAR19+T cell expansion, there was no statistic difference of CAR19+T cell subsets between the complete response group and the incomplete response group. After 6 months, the percentage of CD4+T cells (CD3+CD4+CD8-) in CAR19-T cells in patients was lower than the pre-treatment level(48.0+27.2,63.1+19.7,<0.01), and the percentages of CD197+CD45RA+and CD197-CD45RA-subsets recovered to the pre-treatment level, while the percentage of CD197-CD45RA+subset(4.2+3.0,21.1+15.6,<0.01) was lower than the pre-treatment level. The percentage of CD8+T cells (CD3+CD4-CD8+) returned to pre-treatment level after 6 months, CD197-CD45RA-subset in CD8+T cells returned to pre-treatment level, while CD197+CD45RA+subset(16.6+8.7,35.1+30.1,<0.01),CD197+CD45RA-subset(18.7+9.1,25.8+19.1,<0.01) were still lower than pre-treatment level.

ConclusionAfter CAR19 T cell treatment, there was no significant differences in the proportions of CAR19+T cell subsets in patients with different therapeutic effects. After treatment, the proportion of CAR19-CD3+CD4-CD8+cells recovered earlier than CD3+CD4+CD8-cells, and the dynamic changes of each subgroup were different. This therapeutic regimen has a great impact on the subpopulation of CAR19-T cells in vivo, and the reconstruction of such T cells takes a long time.

Acute lymphoblastic leukemia;Lymphoma;Immune cell therapy;T lymphocytes
Zhu Mingqing, Email: nc.defudabe.adusgniqgnimuhz
引用本文

戴兰,梅仁,沈文红,等. B系肿瘤患者CAR19 T 细胞治疗后体内T细胞增殖的动力学特征[J]. 中华检验医学杂志,2024,47(12):1435-1441.

DOI:10.3760/cma.j.cn114452-20240730-00417

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嵌合抗原受体(chimeric antigen receptor,CAR)T细胞免疫疗法,是近年被认为最有前景的肿瘤治疗方式之一。CAR T细胞治疗技术,主要通过T细胞表达肿瘤抗原受体,使其具有对肿瘤抗原高度亲和性及对抗原负载细胞高效杀伤特性,从而清除肿瘤细胞。在血液肿瘤,尤其是B系肿瘤的治疗上有着显著的疗效 1 , 2。迄今为止,已经有8种CAR T细胞上市,用来治疗复发/难治性(refractory/recurrence,R/R)非霍奇金淋巴瘤(non-Hodgkin lymphoma,NHL)、急性B淋巴细胞白血病(acute B lymphoblastic leukemia,B-ALL)和多发性骨髓瘤 3 , 4 , 5。但对于细胞治疗过程中,CAR T细胞在体内扩增的情况,以及治疗后体内T细胞动态变化规律,未检索到相关文献。
本研究应用二代CAR19 T细胞对入组R/R B系ALL和NHL患者进行了治疗。监测患者输注CAR19 T细胞前后的CAR19+T细胞及体内CAR19-T细胞各亚群,并进行治疗后的疗效评估。观察CAR19-T细胞治疗R/R B系肿瘤过程中,CAR19+T细胞不同亚群的增殖情况和患者体内CAR19-T细胞亚群的水平,及其与治疗效果之间的相关性。
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备注信息
A
朱明清,Email: nc.defudabe.adusgniqgnimuhz
B

戴兰:酝酿和设计实验并进行文章的撰写;梅仁、沈文红、朱子玲、蔡梦洁:实施研究、采集数据;平娜娜、钱崇升:临床资料的整理/分析,临床标本的收集;何林燕:数据的整理和统计分析;白霞:行政、技术及材料支持;朱明清:获取研究经费、起草文章、对文章的知识性内容作批评性审阅

C
戴兰, 梅仁, 沈文红, 等. B系肿瘤患者CAR19 T 细胞治疗后体内T细胞增殖的动力学特征[J]. 中华检验医学杂志, 2024, 47(12): 1435-1441. DOI: 10.3760/cma.j.cn114452-20240730-00417.
D
所有作者声明无利益冲突
E
教育部工程研究中心开放课题 (SDGC2318)
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