Nanoscale CAR Organization at the Immune Synapse Correlates with CAR-T Effector Functions.
CAR-T
CD138
CD45
adoptive cell immunotherapy
cancer
immune synapse
nanoclusters
super resolution microscopy
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
12 09 2023
12 09 2023
Historique:
received:
01
08
2023
revised:
03
09
2023
accepted:
08
09
2023
medline:
4
10
2023
pubmed:
28
9
2023
entrez:
28
9
2023
Statut:
epublish
Résumé
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
Identifiants
pubmed: 37759484
pii: cells12182261
doi: 10.3390/cells12182261
pmc: PMC10527520
pii:
doi:
Substances chimiques
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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