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抗原 (-) 肿瘤细胞变体的定量与功能评估

英文原题:Quantification and functional assessment of antigen(-) tumor cell variants.

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Quantification and functional assessment of antigen(-) tumor cell variants.

PubMed 2025/04/12(内容时间) Methods Cell Biol

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中文摘要

CAR-T 细胞和双特异性抗体(bsAb)等重定向T细胞疗法,可在靶细胞与效应细胞之间形成免疫突触,是癌症免疫治疗的前沿手段。这些疗法施加的选择压力可能使抗原阴性(Ag⁻)或低表达(Ag低)肿瘤细胞变异株富集;此类细胞对治疗耐药,并可能驱动临床复发,即抗原逃逸。接受免疫治疗前,肿瘤组织中通常已存在Ag低/阴性细胞。因此,抗原逃逸是肿瘤生存的重要组成部分,也是需要克服的重大障碍。本文介绍一种定量分析并评估Ag⁻肿瘤细胞功能的方法。该方法可高通量筛查单细胞活检或外周血单个核细胞(PBMC)样本,并通过简单的体外实验评估其被靶向的可能性。本文所述方法可根据需要调整,并应用于不同解剖部位来源样本的研究,也可整合至更大的流式细胞术检测面板,开展全面表型分析。

展开英文摘要原文

T-cell redirecting therapies such as chimeric antigen receptor (CAR) T cells and bispecific antibodies (bsAbs) creating an immunological synapse between target and effector cells are at the forefront of cancer immunotherapies. Selective pressure by these therapies can cause the enrichment of antigen negative (Ag) low / - tumor cell variants which are resistant to therapy and may drive clinical relapse, i. e. Ag escape. Ag low/- cells generally exist in the tumor tissue prior to immunotherapies.

Therefore, Ag escape is an integral part of tumor survival and poses a significant hurdle to overcome.

Here we describe an approach used to quantify and functionally assess Ag - tumor cells. This method enables high-throughput screening of single-cell biopsy or PBMC samples and allows for the assessment of their propensity to be targeted in a straightforward in vitro assay. Methods described here can be modulated and be incorporated to study samples derived from different anatomical locations and can be incorporated in a larger panel of flow cytometry for extensive phenotyping.

论文信息

作者
Odak I、Xie X、Pantsulaia G、Brody J
第一作者单位
Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address: ivan.odak@mssm.edu.United States
通讯作者单位
Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address: joshua.brody@mssm.edu.United States
期刊
Methods in cell biology2026
原文标识
PubMed 41620284 · DOI 10.1016/bs.mcb.2025.03.012