Finding Your CAR

IF 4.7 2区 医学 Q1 PATHOLOGY American Journal of Pathology Pub Date : 2024-08-01 DOI:10.1016/j.ajpath.2024.04.002
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引用次数: 0

Abstract

Adoptive cellular therapy using chimeric antigen receptors (CARs) has transformed immunotherapy by engineering T cells to target specific antigens on tumor cells. As the field continues to advance, pathology laboratories will play increasingly essential roles in the complicated multi-step process of CAR T-cell therapy. These include detection of targetable tumor antigens by flow cytometry or immunohistochemistry at the time of disease diagnosis and the isolation and infusion of CAR T cells. Additional roles include: i) detecting antigen loss or heterogeneity that renders resistance to CAR T cells as well as identifying alternative targetable antigens on tumor cells, ii) monitoring the phenotype, persistence, and tumor infiltration properties of CAR T cells and the tumor microenvironment for factors that predict CAR T-cell therapy success, and iii) evaluating side effects and biomarkers of CAR T-cell cytotoxicity such as cytokine release syndrome. This review highlights existing technologies that are applicable to monitoring CAR T-cell persistence, target antigen identification, and loss. Also discussed are emerging technologies that address new challenges such as how to put a brake on CAR T cells. Although pathology laboratories have already provided companion diagnostic tests important in immunotherapy (eg, programmed death-ligand 1, microsatellite instability, and human epidermal growth factor receptor 2 testing), it draws attention to the exciting new translational research opportunities in adoptive cellular therapy.

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寻找你的 CAR:工程 T 细胞的未来之路。
使用嵌合抗原受体(CAR)的适应性细胞疗法通过改造 T 细胞来靶向肿瘤细胞上的特异性抗原,从而改变了免疫疗法。随着该领域的不断进步,病理实验室将在 CAR-T 疗法复杂的多步骤过程中发挥越来越重要的作用。其中包括在疾病诊断时通过流式细胞术或免疫组化方法检测可靶向的肿瘤抗原,以及分离和输注 CAR-T 细胞。其他作用还包括:(1) 检测导致 CAR-T 抗药性的抗原缺失或异质性,以及识别肿瘤细胞上的替代性可靶向抗原;(2) 监测 CAR T 细胞的表型、持久性和肿瘤浸润特性以及肿瘤微环境,以寻找预测 CAR-T 成功的因素;(3) 评估副作用和 CAR-T 细胞毒性的生物标志物,如细胞因子释放综合征。在本综述中,我们将重点介绍适用于监测 CAR-T 细胞持久性、靶抗原识别和丢失的现有技术。我们还讨论了应对新挑战的新兴技术,如如何抑制 CAR T 细胞。病理实验室已经提供了对免疫疗法非常重要的辅助诊断检测,如 PD-L1、MSI 和 HER2 检测,同时我们也提请大家注意领养细胞疗法中令人兴奋的新转化研究机会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
期刊介绍: The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.
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