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Nanoscale CAR Organization at the Immune Synapse Correlates with CAR-T Effector Functions.
- Source :
-
Cells (2073-4409) . Sep2023, Vol. 12 Issue 18, p2261. 17p. - Publication Year :
- 2023
-
Abstract
- T cells expressing chimeric antigen receptors (CARs) are at the forefront of clinical treatment of cancers. Still, the nanoscale organization of CARs at the interface of CAR-Ts with target cells, which is essential for TCR-mediated T cell activation, remains poorly understood. Here, we studied the nanoscale organization of CARs targeting CD138 proteoglycans in such fixed and live interfaces, generated optimally for single-molecule localization microscopy. CARs showed significant self-association in nanoclusters that was enhanced in interfaces with on-target cells (SKOV-3, CAG, FaDu) relative to negative cells (OVCAR-3). CARs also segregated more efficiently from the abundant membrane phosphatase CD45 in CAR-T cells forming such interfaces. CAR clustering and segregation from CD45 correlated with the effector functions of Ca++ influx and target cell killing. Our results shed new light on the nanoscale organization of CARs on the surfaces of CAR-Ts engaging on- and off-target cells, and its potential significance for CAR-Ts' efficacy and safety. [ABSTRACT FROM AUTHOR]
- Subjects :
- *IMMUNE response
*CHIMERIC antigen receptors
*SYNAPSES
*T cells
*KILLER cells
Subjects
Details
- Language :
- English
- ISSN :
- 20734409
- Volume :
- 12
- Issue :
- 18
- Database :
- Academic Search Index
- Journal :
- Cells (2073-4409)
- Publication Type :
- Academic Journal
- Accession number :
- 172411136
- Full Text :
- https://doi.org/10.3390/cells12182261