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  

Kinetic characteristics of T cell expansion in patients with B tumor after CAR19 T cell therapy

作　　者：戴兰[1] 梅仁 沈文红[1] 朱子玲[1] 蔡梦洁 平娜娜[1] 钱崇升 何林燕 白霞[1] 朱明清[1] Dai Lan;Mei Ren;Shen Wenhong;Zhu Ziling;Cai Mengjie;Ping Nana;Qian Chongsheng;He Linyan;Bai Xia;ZhuMingqing(Jiangsu Institute of Hematology,National Clinical Research Center for Hematologic Diseases,the First Affiliated Hospital of Soochow University,Suzhou 215006,China)

机构地区：[1]苏州大学附属第一医院,江苏省血液研究所,国家血液系统疾病临床医学研究中心,苏州215006

出　　处：《中华检验医学杂志》2024年第12期1435-1441,共7页Chinese Journal of Laboratory Medicine

基　　金：教育部工程研究中心开放课题(SDGC2318)。

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。Objective:To investigate the proliferation kinetics of T cells in patients with B-cell hematologic malignancies who received CAR19 T cell therapy.Methods:Observational 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.Results:At 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.Conclusion:After 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 diffe

关 键 词：急性淋巴细胞白血病 淋巴瘤 免疫细胞治疗 T淋巴细胞 

分 类 号：R733.1[医药卫生—肿瘤]