Immunological Synapse Predicts Effectiveness of Chimeric Antigen Receptor Cells

Wei Xiong, Yuhui Chen, Xi Kang, Zhiying Chen, Peilin Zheng, Yi Hsin Hsu, Joon Hee Jang, Lidong Qin, Hao Liu, Gianpietro Dotti, Dongfang Liu

Research output: Contribution to journalArticle

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)963-975
Number of pages13
JournalMolecular Therapy
Volume26
Issue number4
DOIs
StatePublished - Apr 4 2018

Keywords

  • 4-1BB
  • CD19
  • Kappa
  • T cell
  • chimeric antigen receptor
  • immunological synapse
  • immunotherapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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  • Cite this

    Xiong, W., Chen, Y., Kang, X., Chen, Z., Zheng, P., Hsu, Y. H., Jang, J. H., Qin, L., Liu, H., Dotti, G., & Liu, D. (2018). Immunological Synapse Predicts Effectiveness of Chimeric Antigen Receptor Cells. Molecular Therapy, 26(4), 963-975. https://doi.org/10.1016/j.ymthe.2018.01.020