The physical landscape of CAR-T synapse

Yiwei Xiong; Kendra A Libby; Xiaolei Su

doi:10.1016/j.bpj.2023.09.004

The physical landscape of CAR-T synapse

Biophys J. 2023 Sep 15:S0006-3495(23)00581-7. doi: 10.1016/j.bpj.2023.09.004. Online ahead of print.

Authors

Yiwei Xiong¹, Kendra A Libby², Xiaolei Su³

Affiliations

¹ Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut.
² Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts.
³ Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut; Yale Cancer Center, Yale University, New Haven, Connecticut; Yale Stem Cell Center, Yale University, New Haven, Connecticut. Electronic address: xiaolei.su@yale.edu.

PMID: 37715447
DOI: 10.1016/j.bpj.2023.09.004

Abstract

Chimeric antigen receptor (CAR)-T cells form dynamic immunological synapses with their cancer cell targets. After a CAR-antigen engagement, the CAR-T synapse forms, matures, and finally disassembles, accompanied by substantial remodeling of cell surface proteins, lipids, and glycans. In this review, we provide perspectives for understanding protein distribution, membrane topology, and force transmission across the CAR-T synapse. We highlight the features of CAR-T synapses that differ from T cell receptor synapses, including the disorganized protein pattern, adjustable synapse width, diverse mechano-responding properties, and resulting signaling consequences. Through a range of examples, we illustrate how revealing the biophysical nature of the CAR-T synapse could guide the design of CAR-Ts with improved anti-tumor function.

Publication types

Review

Grants and funding

R35 GM138299/GM/NIGMS NIH HHS/United States