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过继性T细胞疗法:T细胞受体与嵌合抗原受体的比较

Adoptive T Cell Therapies: A Comparison of T Cell Receptors and Chimeric Antigen Receptors.

作者信息

Harris Daniel T, Kranz David M

机构信息

Department of Biochemistry, University of Illinois, 600 S. Matthews Avenue, Urbana, IL 61801, USA.

Department of Biochemistry, University of Illinois, 600 S. Matthews Avenue, Urbana, IL 61801, USA.

出版信息

Trends Pharmacol Sci. 2016 Mar;37(3):220-230. doi: 10.1016/j.tips.2015.11.004. Epub 2015 Dec 17.


DOI:10.1016/j.tips.2015.11.004
PMID:26705086
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4764454/
Abstract

The tumor-killing properties of T cells provide tremendous opportunities to treat cancer. Adoptive T cell therapies have begun to harness this potential by endowing a functionally diverse repertoire of T cells with genetically modified, tumor-specific recognition receptors. Normally, this antigen recognition function is mediated by an αβ T cell receptor (TCR), but the dominant therapeutic forms currently in development are synthetic constructs called chimeric antigen receptors (CARs). While CAR-based adoptive cell therapies are already showing great promise, their basic mechanistic properties have been studied in less detail compared with those of αβ TCRs. In this review, we compare and contrast various features of TCRs versus CARs, with a goal of highlighting issues that need to be addressed to fully exploit the therapeutic potential of both.

摘要

T细胞的肿瘤杀伤特性为癌症治疗提供了巨大机遇。过继性T细胞疗法已开始通过赋予功能多样的T细胞库以经基因改造的肿瘤特异性识别受体来利用这一潜力。正常情况下,这种抗原识别功能由αβ T细胞受体(TCR)介导,但目前正在研发的主要治疗形式是一种名为嵌合抗原受体(CAR)的合成构建体。虽然基于CAR的过继性细胞疗法已显示出巨大前景,但与αβ TCR相比,对其基本机制特性的研究还不够详细。在本综述中,我们比较并对比了TCR与CAR的各种特征,目的是突出充分发挥两者治疗潜力所需解决的问题。

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[8]
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[10]
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本文引用的文献

[1]
Affinity-Tuned ErbB2 or EGFR Chimeric Antigen Receptor T Cells Exhibit an Increased Therapeutic Index against Tumors in Mice.

Cancer Res. 2015-9-1

[2]
Tuning Sensitivity of CAR to EGFR Density Limits Recognition of Normal Tissue While Maintaining Potent Antitumor Activity.

Cancer Res. 2015-9-1

[3]
CD19 CAR Therapy for Acute Lymphoblastic Leukemia.

Am Soc Clin Oncol Educ Book. 2015

[4]
4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors.

Nat Med. 2015-6

[5]
Chimeric antigen receptor T cells for cancer immunotherapy.

J Clin Oncol. 2015-5-20

[6]
Adoptive cellular therapy: a race to the finish line.

Sci Transl Med. 2015-3-25

[7]
Targeting cancer-specific mutations by T cell receptor gene therapy.

Curr Opin Immunol. 2015-4

[8]
The interplay of effector and regulatory T cells in cancer.

Curr Opin Immunol. 2015-2-27

[9]
Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma.

Sci Transl Med. 2015-2-18

[10]
The role of T cell receptor signaling thresholds in guiding T cell fate decisions.

Curr Opin Immunol. 2015-4

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