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下一代嵌合抗原受体 T 细胞：克服毒性的安全策略。

Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity.

机构信息

Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China.

出版信息

Mol Cancer. 2019 Aug 20;18(1):125. doi: 10.1186/s12943-019-1057-4.

DOI:10.1186/s12943-019-1057-4
PMID:31429760
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6701025/
Abstract

Chimeric antigen receptor T (CAR-T) cell therapy is an emerging and effective cancer immunotherapy. Especially in hematological malignancies, CAR-T cells have achieved exciting results. Two Anti-CD19 CAR-T therapies have been approved for the treatment of CD19-positive leukemia or lymphoma. However, the application of CAR-T cells is obviously hampered by the adverse effects, such as cytokines release syndrome and on-target off-tumor toxicity. In some clinical trials, patients quitted the treatment of CAR-T cells due to life-threatening toxicity. Seeking to alleviate these toxicities or prevent the occurrence, researchers have developed a number of safety strategies of CAR-T cells, including suicide genes, synthetic Notch receptor, on-switch CAR, combinatorial target-antigen recognition, bispecific T cell engager and inhibitory CAR. This review summarized the preclinical studies and clinical trials of the safety strategies of CAR-T cells and their respective strengths and weaknesses.

摘要

嵌合抗原受体 T (CAR-T) 细胞疗法是一种新兴且有效的癌症免疫疗法。特别是在血液恶性肿瘤中，CAR-T 细胞已经取得了令人兴奋的成果。两种抗 CD19 CAR-T 疗法已被批准用于治疗 CD19 阳性白血病或淋巴瘤。然而，CAR-T 细胞的应用明显受到细胞因子释放综合征和脱靶毒性等不良反应的限制。在一些临床试验中，由于危及生命的毒性，患者停止了 CAR-T 细胞的治疗。为了减轻这些毒性或预防其发生，研究人员开发了许多 CAR-T 细胞的安全策略，包括自杀基因、合成 Notch 受体、开关型 CAR、组合靶抗原识别、双特异性 T 细胞衔接子和抑制性 CAR。本综述总结了 CAR-T 细胞安全策略的临床前研究和临床试验及其各自的优缺点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/674a/6701025/9e67ee1748c4/12943_2019_1057_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/674a/6701025/9e67ee1748c4/12943_2019_1057_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/674a/6701025/9e67ee1748c4/12943_2019_1057_Fig1_HTML.jpg

相似文献

[1]
Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity.

Mol Cancer. 2019-8-20

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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Trends Cancer. 2019-10

[10]
Immune Cell Hacking: Challenges and Clinical Approaches to Create Smarter Generations of Chimeric Antigen Receptor T Cells.

Front Immunol. 2018-7-31

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本文引用的文献

[1]
Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory.

Cell. 2019-4-4

[2]
Logic-Gated ROR1 Chimeric Antigen Receptor Expression Rescues T Cell-Mediated Toxicity to Normal Tissues and Enables Selective Tumor Targeting.

Cancer Cell. 2019-3-18

[3]
Preclinical Development of Bivalent Chimeric Antigen Receptors Targeting Both CD19 and CD22.

Mol Ther Oncolytics. 2018-11-6

[4]
CML Hematopoietic Stem Cells Expressing IL1RAP Can Be Targeted by Chimeric Antigen Receptor-Engineered T Cells.

Cancer Res. 2018-12-4

[5]
Chimeric antigen receptors: unleashing a new age of anti-cancer therapy.

Cancer Cell Int. 2018-11-14

[6]
Cytokine release syndrome: grading, modeling, and new therapy.

J Hematol Oncol. 2018-9-24

[7]
TanCAR T cells targeting CD19 and CD133 efficiently eliminate MLL leukemic cells.

Leukemia. 2018-9

[8]
Immunotherapy with CAR-Modified T Cells: Toxicities and Overcoming Strategies.

J Immunol Res. 2018-4-17

[9]
Extracellular NGFR Spacers Allow Efficient Tracking and Enrichment of Fully Functional CAR-T Cells Co-Expressing a Suicide Gene.

Front Immunol. 2018-3-21

[10]
Gut microbiome modulates efficacy of immune checkpoint inhibitors.

J Hematol Oncol. 2018-3-27

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