抗CD19嵌合抗原受体T细胞IM19在B细胞肿瘤中的安全性及疗效研究  

Efficacy and safety of anti-CD 19 chimeric antigen receptor T cells IM19 in B cell hematologic malignancies

作　　者：应志涛[1] 张弦 宋玉琴[1] 杨君芳 王小沛[1] 郑文[1] 林宁晶[1] 涂梅峰[1] 谢彦[1] 平凌燕 张晨[1] 刘卫平[1] 邓丽娟[1] 吴非 鲁薪安 何霆 齐菲菲 陆佩华 朱军[1] YING Zhi-tao;ZHANG Xian;SONG Yu-qin;YANG Jun-fang;WANG Xiao-pei;ZHENG Wen;LIN Ning-jing;TU Mei-feng;XIE Yan;PING Ling-yan;ZHANG Chen;LIU Wei-ping;DENG Li-juan;WU Fei;LU Xin-an;HE Ting;QI Fei-fei;LU Pei-hua;ZHU Jun(Department of Lymphoma , Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education),Peking University Cancer Hospital & Institute, Beijing 100142,China;Hebei Yanda Lu Daopei Hospital,Langfang 065201,China;Beijing Immunochina Pharmaceuticals,Co.,Ltd.,Beijing 100195,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所淋巴瘤科恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142 [2]河北燕达陆道培医院,廊坊065201 [3]北京艺妙神州医药科技有限公司,北京100195

出　　处：《中国新药杂志》2019年第6期689-696,共8页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(81600164);北京市自然科学基金资助项目(7172046);北京市属医院科研培育计划资助项目(PX2017001)

摘　　要：目的:评价抗CD19嵌合抗原受体T(chimeric antigen receptor T,CAR-T)细胞IM19在复发难治B细胞血液系统恶性肿瘤中的疗效及安全性。方法:12例复发难治B细胞血液系统恶性肿瘤患者接受IM19治疗,包括6例B细胞非霍奇金淋巴瘤和6例急性B淋巴细胞白血病患者。患者接受3×10~5～10×10~5cells·kg^(-1)CAR-T细胞输注。细胞回输后1和3个月评估疗效,并监测不良反应事件的发生情况,同时检测细胞扩增以及细胞因子释放。结果:12例患者中有11例达到完全缓解,患者体内可以检测到IM19扩增,以及白介素-6和白介素-10水平升高。没有患者发生≥3级的细胞因子释放综合征和CAR-T细胞相关的神经系统毒性。结论:IM19治疗复发难治B细胞血液系统恶性肿瘤安全有效。Objective: To investigate the therapeutic efficacy and adverse events of IM19 chimeric antigen receptor T cells in relapsed or refractory B cell hematologic malignancies. Methods: Twelve patients with relapsed or refractory B-cell malignancies, including six B cell Non-Hodgkin lymphoma and six acute lymphoblastic leukemia patients, received IM 19 infusion at dose of 3 × 10^5 ~ 10 × 10^5 cells · kg^-1 IM19. All patients were followed up by monitoring tumor burden ( at 1 and 3 month after infusion), CAR-T persistence, cytokines and adverse events. Results: All but one patients achieved complete remission. IM 19 cells proliferated in vivo and were detectable in the blood. Cytokines including interleukin (IL)-6 and IL-10 were increased after CAR-T infusion. No severe cytokine release syndrome ( CRS )(≥grade 3 ) or CAR-T cell-related encephalopathy syndrome ( CRES )(≥ grade 3 ) occurred. Conclusion : IM 19 is associated with a high remission rate and tolerable toxicities.

关 键 词：嵌合抗原受体T细胞 B细胞 非霍奇金淋巴瘤 急性淋巴细胞白血病 细胞因子释放综合征 CAR-T细胞相关神经系统毒性 

分 类 号：R979.1[医药卫生—药品]