@article{d372f9449a9647669b662b11e53c1e52,
title = "Immunological Synapse Predicts Effectiveness of Chimeric Antigen Receptor Cells",
abstract = "Chimeric antigen receptor (CAR)-modified T cell therapy has the potential to improve the overall survival of patients with malignancies by enhancing the effectiveness of CAR T cells. Precisely predicting the effectiveness of various CAR T cells represents one of today's key unsolved problems in immunotherapy. Here, we predict the effectiveness of CAR-modified cells by evaluating the quality of the CAR-mediated immunological synapse (IS) by quantitation of F-actin, clustering of tumor antigen, polarization of lytic granules (LGs), and distribution of key signaling molecules within the IS. Long-term killing capability, but not secretion of conventional cytokines or standard 4-hr cytotoxicity, correlates positively with the quality of the IS in two different CAR T cells that share identical antigen specificity. Xenograft model data confirm that the quality of the IS in vitro correlates positively with performance of CAR-modified immune cells in vivo. Therefore, we propose that the quality of the IS predicts the effectiveness of CAR-modified immune cells, which provides a novel strategy to guide CAR therapy. Xiong et al. developed a novel approach to predict the effectiveness of CAR-modified cells by quantifying the quality of CAR-mediated immunological synapse, which may introduce a new parameter to the field of immunotherapy.",
keywords = "4-1BB, CD19, Kappa, T cell, chimeric antigen receptor, immunological synapse, immunotherapy",
author = "Wei Xiong and Yuhui Chen and Xi Kang and Zhiying Chen and Peilin Zheng and Hsu, {Yi Hsin} and Jang, {Joon Hee} and Lidong Qin and Hao Liu and Gianpietro Dotti and Dongfang Liu",
note = "Funding Information: The authors thank Malcolm K. Brenner, Helen E. Heslop, Carlos A. Ramos, and Jordan S. Orange (Baylor College of Medicine) for helpful discussions and John M. Jerome, Nicole Weber, and Casey Schroeder for critical reading of the manuscript. This work was supported in part by HL125018 from NHLBI (to D.L.), AI124769 from NIAID (to D.L.), AI129594 from NIAID (to D.L.), AI130197 from NIAID (to D.L.), the Houston Methodist Career Cornerstone Award, the Houston Methodist Research Institute for Academic Medicine NIH Competitiveness Initiative Award, the Baylor-UT Houston Center for AIDS Research Core Support Grant (AI036211) from the National Institute of Allergy and Infectious Diseases, the Caroline Wiess Law Fund for Research in Molecular Medicine, the Texas Children's Hospital Pediatric Pilot Research Fund, the Lymphoma SPORE Developmental Research Program from Baylor College of Medicine and the Methodist Research Institute (P50 CA126752), and Celgene research funding. Funding Information: The authors thank Malcolm K. Brenner, Helen E. Heslop, Carlos A. Ramos, and Jordan S. Orange (Baylor College of Medicine) for helpful discussions and John M. Jerome, Nicole Weber, and Casey Schroeder for critical reading of the manuscript. This work was supported in part by HL125018 from NHLBI (to D.L.), AI124769 from NIAID (to D.L.), AI129594 from NIAID (to D.L.), AI130197 from NIAID (to D.L.), the Houston Methodist Career Cornerstone Award, the Houston Methodist Research Institute for Academic Medicine NIH Competitiveness Initiative Award, the Baylor-UT Houston Center for AIDS Research Core Support Grant ( AI036211 ) from the National Institute of Allergy and Infectious Diseases , the Caroline Wiess Law Fund for Research in Molecular Medicine , the Texas Children{\textquoteright}s Hospital Pediatric Pilot Research Fund , the Lymphoma SPORE Developmental Research Program from Baylor College of Medicine and the Methodist Research Institute ( P50 CA126752 ), and Celgene research funding. Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = apr,
day = "4",
doi = "10.1016/j.ymthe.2018.01.020",
language = "English (US)",
volume = "26",
pages = "963--975",
journal = "Molecular therapy : the journal of the American Society of Gene Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "4",
}