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 language | English (US) |
|---|---|
| Pages (from-to) | 963-975 |
| Number of pages | 13 |
| Journal | Molecular Therapy |
| Volume | 26 |
| Issue number | 4 |
| DOIs | |
| State | Published - 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