CAR-T细胞技术在复发或难治急性淋巴细胞白血病中的临床应用进展

花京剩; 张剑; 陈苏宁; 仇惠英

doi:10.13201/j.issn.1004-2806.2020.01.018

CAR-T细胞技术在复发或难治急性淋巴细胞白血病中的临床应用进展

- 1. 苏州大学附属第一医院血液病研究所(江苏苏州, 215006);
- 2. 浙江台州市立医院血液科(浙江台州, 318000)
基金项目:
江苏省科技项目(No:BE2018652)

详细信息

通讯作者: 仇惠英,E-mail:qiuhuiying8303@suda.edu.cn

中图分类号: R733.71

收稿日期: 2019-05-24

Advances in clinical application of CAR-T cell technique in relapsed or refractory acute lymphoblastic leukemia

More Information

Corresponding author: CHOU Huiying, E-mail: qiuhuiying8303@suda.edu.cn

Received Date: 24 May 2019

摘要

摘要: 儿童急性淋巴细胞白血病（acute lymphoblastic leukemia,ALL）在首次复发后5年生存率仅30%～50%[1],初诊成人ALL 5年生存率约40%,复发后的5年生存率仅为10%[2]。近几年Ⅰ期或Ⅱ期临床试验用嵌合抗原受体-T（CAR-T）细胞技术来治疗复发或难治的ALL,取得了令人印象深刻的效果。CAR-T细胞治疗是一种基于细胞水平的靶向治疗,这种个体化的治疗利用了人体T淋巴细胞的天然功能。来自患者或供体的T淋
- CAR-T细胞 /
- B系急性淋巴细胞白血病 /
- 复发或难治 /
- 老年 /
- 不良反应
Abstract: In recent years,CAR-T cell therapy for B-cell hematological malignancies is a new and effective method,and has achieved promising therapeutic effects.Especially for relapsed or refractory B-cell acute lymphoblastic leukemia(B-ALL),the remission rate can reach as high as 90%.CAR-T cell are not widely used because of their complications.CAR-T cell immunotherapy has made rapid progress in the treatment of relapsed or refractory ALL.In this paper,some advances regarding modified design of CAR structure,the results of single-target or combined target antigen therapy for relapsed or refractory ALL,universal CAR-T,relapsed ALL induction and bridging to hematopoietic stem cell transplantation,the role of CAR-T cell in treating the elderly B-lymphoblastic leukemia along with adverse events and management are reviewed.
- CAR-T cell /
- B-line acute lymphoblastic leukemia /
- relapse or refractory /
- elderly /
- adverse events

HTML全文

参考文献(31)

[1]	陆爱东,张乐萍,贾月萍,等.TCF3-HLF融合基因阳性儿童急性淋巴细胞白血病2例并文献复习[J].临床血液学杂志,2018,31(11):862-864.
[2]	Frey NV,Luger SM.How I treat adults with relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia[J].Blood,2015,126:589-596.
[3]	Maude S,Barrett DM.Current status of chimeric antigen receptor therapy for haematological malignancies[J].Br J Haematol,2016,172:11-22.
[4]	Lee DW,Kochenderfer JN,Stetler-Stevenson M,et al.T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults:a phase 1 dose-escalation trial[J].Lancet,2015,385:517-528.
[5]	Karschnia P,Jordan JT,Forst DA,et al.Clinical presentation,management,and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells[J].Blood,2019,133:2212-2221.
[6]	Maude SL,Laetsch TW,Buechner J,et al.Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia[J].N Engl J Med,2018,378:439-448.
[7]	van der Stegen SJ,Hamieh M,Sadelain M.The pharmacology of second-generation chimeric antigen receptors[J].Nat Rev Drug Discov,2015,14:499-509.
[8]	Cherkassky L,Morello A,Villena-Vargas J,et al.Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition[J].J Clin Invest,2016,126:3130-3144.
[9]	Adachi K,Kano Y,Nagai T,et al.IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor[J].Nat Biotechnol,2018,36:346-351.
[10]	Liu J,Zhou G,Zhang L,et al.Building Potent Chimeric Antigen Receptor T Cells With CRISPR Genome Editing[J].Front Immunol,2019,10:456.
[11]	Jacoby E,Yang Y,Qin H,et al.Murine allogeneic CD19 CAR T cells harbor potent antileukemic activity but have the potential to mediate lethal GVHD[J].Blood,2016,127:1361-1370.
[12]	Dunbar CE,High KA,Joung JK,et al.Gene therapy comes of age[J].Science,2018,359(6372).pii:eaan4672.doi:10.1126/science.aan4672.
[13]	Sadelain M,Brentjens R,Riviere I,et al.CD19 CAR Therapy for Acute Lymphoblastic Leukemia[J].Am Soc Clin Oncol Educ Book,2015,2015:e360-e363.
[14]	Park JH,Riviere I,Gonen M,et al.Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia[J].N Engl J Med,2018,378:449-459.
[15]	Cao J,Wang G,Cheng H,et al.Potent anti-leukemia activities of humanized CD19-targeted Chimeric antigen receptor T (CAR-T) cells in patients with relapsed/refractory acute lymphoblastic leukemia[J].Am J Hematol,2018,93:851-858.
[16]	Jiang H,Liu L,Guo T,et al.Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy[J].Ann Hematol,2019,98:1721-1732.
[17]	Fry TJ,Shah NN,Orentas RJ,et al.CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy[J].Nat Med,2018,24:20-28.
[18]	Pan J,Niu Q,Deng B,et al.CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia[J].Leukemia,2019 May 20.doi:10.1038/s41375-019-0488-7.[Epub ahead of print].
[19]	Hu Y,Wu Z,Luo Y,et al.Potent Anti-leukemia Activities of Chimeric Antigen Receptor-Modified T Cells against CD19 in Chinese Patients with Relapsed/Refractory Acute Lymphocytic Leukemia[J].Clin Cancer Res,2017,23:3297-3306.
[20]	Brudno JN,Somerville RP,Shi V,et al.Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease[J].J Clin Oncol,2016,34:1112-1121.
[21]	Qasim W,Zhan H,Samarasinghe S,et al.Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells[J].Sci Transl Med,2017 Feb 15;9(377).pii:aam9292.doi:10.1126/scitranslmed.aam9292.
[22]	Pan J,Yang JF,Deng BP,et al.High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients[J].Leukemia,2017,31:2587-2593.
[23]	Zhang X,Lu XA Yang J.Efficacy and safety of CD19 chimeric antigen receptor (CAR) T cell therapy for B-cell acute lymphocytic leukemia (B-cell ALL) in a large cohort including patients with extramedullary disease(EMD),high leukemia burden,BCR-ABL (+) mutation,TP53 mutation,and post-transplant relapse[J].Blood,2018,132(Suppl 1):280.
[24]	江慧雯,梅恒,刘林,等.CAR-T治疗桥接造血干细胞移植治疗原发难治性急性B淋巴细胞白血病[J].临床血液学杂志,2018,31(9):708-710.
[25]	Zhao Y,Zhang J Liu D.CD19-CAR-T therapy followed by allogeneic hematopoietic stem cell transplantation in refractory/relapsed and High risk B-cell acute lymphoblastic leukemia[J].Blood,2018,132:2660.
[26]	Brown CE,Alizadeh D,Starr R,et al.Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy[J].N Engl J Med,2016,375:2561-2569.
[27]	He X,Xiao X,Li Q,et al.Anti-CD19 CAR-T as a feasible and safe treatment against central nervous system leukemia after intrathecal chemotherapy in adults with relapsed or refractory B-ALL[J].Leukemia,2019,33:2102-2104.
[28]	瞿敏,陶千山,安福润,等.CAR-T治疗复发难治B细胞淋巴瘤的安全性及临床疗效分析[J].临床血液学杂志,2019,32(7):521-526.
[29]	Lee DW,Gardner R,Porter DL,et al.Current concepts in the diagnosis and management of cytokine release syndrome[J].Blood,2014,124:188-195.
[30]	Porter DL,Hwang WT,Frey NV,et al.Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia[J].Sci TranslMed,2015,7:139r-303r.
[31]	Brudno JN,Kochenderfer JN.Toxicities of chimeric antigen receptor T cells:recognition and management[J].Blood,2016,127:3321-3330.