Sue and Bill Gross Stem Cell Research Center, Sue & Bill Gross Hall CIRM Institute, University of California, Irvine, 845 Health Sciences Road, Suite 3027, Irvine, CA 92697, USA.
Lab Chip. 2018 Dec 4;18(24):3733-3749. doi: 10.1039/c8lc00818c.
Adoptive T cell transfer, in particular TCR T cell therapy, holds great promise for cancer immunotherapy with encouraging clinical results. However, finding the right TCR T cell clone is a tedious, time-consuming, and costly process. Thus, there is a critical need for single cell technologies to conduct fast and multiplexed functional analyses followed by recovery of the clone of interest. Here, we use droplet microfluidics for functional screening and real-time monitoring of single TCR T cell activation upon recognition of target tumor cells. Notably, our platform includes a tracking system for each clone as well as a sorting procedure with 100% specificity validated by downstream single cell reverse-transcription PCR and sequencing of TCR chains. Our TCR screening prototype will facilitate immunotherapeutic screening and development of T cell therapies.
过继性 T 细胞转移,特别是 TCR T 细胞疗法,在癌症免疫治疗方面具有广阔的前景,其临床结果令人鼓舞。然而,寻找合适的 TCR T 细胞克隆是一个繁琐、耗时且昂贵的过程。因此,迫切需要单细胞技术来进行快速和多重功能分析,然后回收感兴趣的克隆。在这里,我们使用液滴微流控技术对单个 TCR T 细胞在识别靶肿瘤细胞时的激活进行功能筛选和实时监测。值得注意的是,我们的平台为每个克隆都包括一个跟踪系统,以及一个分选程序,其 100%的特异性通过下游单细胞逆转录 PCR 和 TCR 链测序得到验证。我们的 TCR 筛选原型将促进免疫治疗筛选和 T 细胞疗法的发展。
Lab Chip. 2018-12-4
Methods Enzymol. 2019
Cancer Immunol Res. 2018-3-27
Methods Mol Med. 2005
J Immunother Cancer. 2019-11-5
Biosensors (Basel). 2025-5-29
Nat Commun. 2025-1-2
Proc Natl Acad Sci U S A. 2024-10-29
Anal Chem. 2024-9-17
Exp Hematol Oncol. 2024-4-3
Front Immunol. 2018-7-18
N Engl J Med. 2018-7-5
Gene Ther. 2018-6-7
Nat Biotechnol. 2018-3-6