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嵌合抗原受体疗法在急性淋巴细胞白血病临床实践中的应用

Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice.

作者信息

Luskin Marlise R, DeAngelo Daniel J

机构信息

Harvard Medical School, Boston, MA, USA.

Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.

出版信息

Curr Hematol Malig Rep. 2017 Aug;12(4):370-379. doi: 10.1007/s11899-017-0394-x.


DOI:10.1007/s11899-017-0394-x
PMID:28656487
Abstract

Over half of patients diagnosed with B-cell acute lymphoblastic leukemia (ALL) develop relapsed or refractory disease. Traditional chemotherapy salvage is inadequate, and new therapies are needed. Chimeric antigen receptor (CAR) T cell therapy is a novel, immunologic approach where T cells are genetically engineered to express a CAR conferring specificity against a target cell surface antigen, most commonly the pan-B-cell marker CD19. After infusion, CAR T cells expand and persist, allowing ongoing tumor surveillance. Several anti-CD19 CAR T cell constructs have induced high response rates in heavily pre-treated populations, although durability of response varied. Severe toxicity (cytokine release syndrome and neurotoxicity) is the primary constraint to broad implementation of CAR T cell therapy. Here, we review the experience of CAR T cell therapy for ALL and ongoing efforts to modify existing technology to improve efficacy and decrease toxicity. As an anti-CD19 CAR T cell construct may be FDA approved soon, we focus on issues relevant to practicing clinicians.

摘要

超过半数被诊断为B细胞急性淋巴细胞白血病(ALL)的患者会出现复发或难治性疾病。传统的化疗挽救方案并不充分,因此需要新的治疗方法。嵌合抗原受体(CAR)T细胞疗法是一种新型的免疫疗法,通过基因工程改造T细胞,使其表达一种针对靶细胞表面抗原(最常见的是泛B细胞标志物CD19)的CAR。输注后,CAR T细胞会扩增并持续存在,从而实现持续的肿瘤监测。尽管反应的持久性各不相同,但几种抗CD19 CAR T细胞构建体已在经过大量预处理的人群中诱导出了高反应率。严重毒性(细胞因子释放综合征和神经毒性)是CAR T细胞疗法广泛应用的主要限制因素。在此,我们回顾了CAR T细胞疗法治疗ALL的经验,以及为改进现有技术以提高疗效和降低毒性而正在进行的努力。由于一种抗CD19 CAR T细胞构建体可能很快会获得美国食品药品监督管理局(FDA)的批准,我们重点关注与临床医生实践相关的问题。

相似文献

[1]
Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice.

Curr Hematol Malig Rep. 2017-8

[2]
An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T (CAR-T) cells.

Sci China Life Sci. 2016-3-24

[3]
Redirecting T cells to eradicate B-cell acute lymphoblastic leukemia: bispecific T-cell engagers and chimeric antigen receptors.

Leukemia. 2016-12-28

[4]
CAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia.

Curr Treat Options Oncol. 2016-6

[5]
CAR T-cell therapy is effective for CD19-dim B-lymphoblastic leukemia but is impacted by prior blinatumomab therapy.

Blood Adv. 2019-11-26

[6]
CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies?

Immunotherapy. 2015

[7]
Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia.

J Hematol Oncol. 2016-11-25

[8]
The what, when and how of CAR T cell therapy for ALL.

Best Pract Res Clin Haematol. 2017-9

[9]
CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia.

Clin Adv Hematol Oncol. 2016-10

[10]
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Front Immunol. 2020

引用本文的文献

[1]
Resistance against anti-CD19 and anti-BCMA CAR T cells: Recent advances and coping strategies.

Transl Oncol. 2022-8

[2]
[Maintenance therapy following CD19 CAR-T treatment for relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Zhonghua Xue Ye Xue Za Zhi. 2020-6-14

[3]
Approach to the Adult Acute Lymphoblastic Leukemia Patient.

J Clin Med. 2019-8-6

[4]
[Construction and in vitro verification of a new humanized anti-CD19 CAR-T cells with high affinity].

Zhonghua Xue Ye Xue Za Zhi. 2018-6-14

[5]
Genetically enhanced T lymphocytes and the intensive care unit.

Oncotarget. 2018-3-27

[6]
Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia.

Front Immunol. 2018-2-19

[7]
Re-Emergence of Dendritic Cell Vaccines for Cancer Treatment.

Trends Cancer. 2018-2

[8]
The future of immune checkpoint blockade immunotherapy: towards personalized therapy or towards combination therapy.

J Thorac Dis. 2017-11

[9]
[Progress in clinical studies of chimeric antigen receptor engineered T cells for treatment of childhood cancer].

Zhongguo Dang Dai Er Ke Za Zhi. 2017-11

本文引用的文献

[1]
Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia.

N Engl J Med. 2017-3-2

[2]
Cytokine release syndrome with novel therapeutics for acute lymphoblastic leukemia.

Hematology Am Soc Hematol Educ Program. 2016-12-2

[3]
Chimeric Antigen Receptor T cells for B Cell Neoplasms: Choose the Right CAR for You.

Curr Hematol Malig Rep. 2016-10

[4]
Remote Controlled CARs: Towards a Safer Therapy for Leukemia.

Cancer Immunol Res. 2016-6-23

[5]
A Tet-On Inducible System for Controlling CD19-Chimeric Antigen Receptor Expression upon Drug Administration.

Cancer Immunol Res. 2016-6-21

[6]
Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia.

N Engl J Med. 2016-8-25

[7]
CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date.

Blood. 2016-6-30

[8]
CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients.

J Clin Invest. 2016-6-1

[9]
Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia.

Cancer Discov. 2016-6

[10]
Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy.

Biochem Soc Trans. 2016-4-15

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