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针对 CAR T 细胞疗法的可靶向生物标志物的扩展。

The expansion of targetable biomarkers for CAR T cell therapy.

机构信息

Department of Microbiology and Molecular Biology, Brigham Young University, 3142 LSB, Provo, UT, 84602, USA.

Thunder Biotech, Highland, UT, USA.

出版信息

J Exp Clin Cancer Res. 2018 Jul 21;37(1):163. doi: 10.1186/s13046-018-0817-0.

DOI:10.1186/s13046-018-0817-0
PMID:30031396
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6054736/
Abstract

Biomarkers are an integral part of cancer management due to their use in risk assessment, screening, differential diagnosis, prognosis, prediction of response to treatment, and monitoring progress of disease. Recently, with the advent of Chimeric Antigen Receptor (CAR) T cell therapy, a new category of targetable biomarkers has emerged. These biomarkers are associated with the surface of malignant cells and serve as targets for directing cytotoxic T cells. The first biomarker target used for CAR T cell therapy was CD19, a B cell marker expressed highly on malignant B cells. With the success of CD19, the last decade has shown an explosion of new targetable biomarkers on a range of human malignancies. These surface targets have made it possible to provide directed, specific therapy that reduces healthy tissue destruction and preserves the patient's immune system during treatment. As of May 2018, there are over 100 clinical trials underway that target over 25 different surface biomarkers in almost every human tissue. This expansion has led to not only promising results in terms of patient outcome, but has also led to an exponential growth in the investigation of new biomarkers that could potentially be utilized in CAR T cell therapy for treating patients. In this review, we discuss the biomarkers currently under investigation and point out several promising biomarkers in the preclinical stage of development that may be useful as targets.

摘要

生物标志物是癌症管理的一个组成部分,因为它们可用于风险评估、筛查、鉴别诊断、预后、预测治疗反应以及监测疾病进展。最近,随着嵌合抗原受体 (CAR) T 细胞疗法的出现,出现了一类新的可靶向生物标志物。这些生物标志物与恶性细胞的表面有关,可作为引导细胞毒性 T 细胞的靶点。用于 CAR T 细胞疗法的第一个生物标志物靶标是 CD19,这是一种在恶性 B 细胞上高度表达的 B 细胞标志物。随着 CD19 的成功,过去十年在一系列人类恶性肿瘤中出现了大量新的可靶向生物标志物。这些表面靶点使得可以提供定向、特异性的治疗,减少健康组织的破坏,并在治疗过程中保留患者的免疫系统。截至 2018 年 5 月,正在进行的临床试验超过 100 项,针对几乎每种人体组织中的超过 25 种不同的表面生物标志物。这种扩张不仅带来了患者预后方面的有希望的结果,而且还导致了对新生物标志物的研究呈指数级增长,这些新生物标志物有可能用于 CAR T 细胞疗法治疗患者。在这篇综述中,我们讨论了目前正在研究的生物标志物,并指出了几个在临床前开发阶段具有前景的有希望的生物标志物,这些标志物可能作为靶点有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/6054736/ccaaa7e198ca/13046_2018_817_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/6054736/00c27cb2e5b4/13046_2018_817_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/6054736/01bd6b3992c5/13046_2018_817_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/6054736/03419f9d275c/13046_2018_817_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/6054736/3310acece554/13046_2018_817_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/6054736/ccaaa7e198ca/13046_2018_817_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/6054736/00c27cb2e5b4/13046_2018_817_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/6054736/01bd6b3992c5/13046_2018_817_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/6054736/03419f9d275c/13046_2018_817_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/6054736/3310acece554/13046_2018_817_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/6054736/ccaaa7e198ca/13046_2018_817_Fig5_HTML.jpg

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