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治疗性T细胞工程

Therapeutic T cell engineering.

作者信息

Sadelain Michel, Rivière Isabelle, Riddell Stanley

机构信息

Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.

Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.

出版信息

Nature. 2017 May 24;545(7655):423-431. doi: 10.1038/nature22395.


DOI:10.1038/nature22395
PMID:28541315
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5632949/
Abstract

Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimaeric antigen receptors (CARs) are a class of synthetic receptors that reprogram lymphocyte specificity and function. CARs targeting CD19 have demonstrated remarkable potency in B cell malignancies. Engineered T cells are applicable in principle to many cancers, pending further progress to identify suitable target antigens, overcome immunosuppressive tumour microenvironments, reduce toxicities, and prevent antigen escape. Advances in the selection of optimal T cells, genetic engineering, and cell manufacturing are poised to broaden T-cell-based therapies and foster new applications in infectious diseases and autoimmunity.

摘要

基因工程改造的T细胞是强大的新型药物,为癌症患者带来了治愈的希望。嵌合抗原受体(CAR)是一类可重新编程淋巴细胞特异性和功能的合成受体。靶向CD19的CAR在B细胞恶性肿瘤中已显示出显著疗效。从原理上讲,工程化T细胞适用于多种癌症,但仍需进一步取得进展以确定合适的靶抗原、克服免疫抑制性肿瘤微环境、降低毒性并防止抗原逃逸。在最佳T细胞选择、基因工程和细胞制造方面的进展有望拓宽基于T细胞的疗法,并在传染病和自身免疫性疾病中催生新的应用。

相似文献

[1]
Therapeutic T cell engineering.

Nature. 2017-5-24

[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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Front Biosci (Landmark Ed). 2017-6-1

[10]
Enhanced Cancer Immunotherapy by Chimeric Antigen Receptor-Modified T Cells Engineered to Secrete Checkpoint Inhibitors.

Clin Cancer Res. 2017-9-14

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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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[10]
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本文引用的文献

[1]
An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity.

Mol Ther Oncolytics. 2017-1-11

[2]
Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection.

Nature. 2017-3-2

[3]
Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells.

Sci Transl Med. 2017-1-25

[4]
Anti-CD22 CAR Therapy Leads to ALL Remissions.

Cancer Discov. 2017-1-9

[5]
Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity.

Nat Med. 2017-2

[6]
PD-1 blockade modulates chimeric antigen receptor (CAR)-modified T cells: refueling the CAR.

Blood. 2017-2-23

[7]
Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy.

N Engl J Med. 2016-12-29

[8]
Expression of a Chimeric Antigen Receptor Specific for Donor HLA Class I Enhances the Potency of Human Regulatory T Cells in Preventing Human Skin Transplant Rejection.

Am J Transplant. 2017-4

[9]
Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues.

Clin Cancer Res. 2017-6-15

[10]
Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia.

J Clin Invest. 2016-11-1

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