Nanoscale CAR Organization at the Immune Synapse Correlates with CAR-T Effector Functions

Autor: Julia Sajman, Oren Yakovian, Naamit Unger Deshet, Shaked Almog, Galit Horn, Tova Waks, Anat Globerson Levin, Eilon Sherman
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cells, Vol 12, Iss 18, p 2261 (2023)
Druh dokumentu: article
ISSN: 2073-4409
DOI: 10.3390/cells12182261
Popis: 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.
Databáze: Directory of Open Access Journals
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