REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1664403
This article is part of the Research TopicExploring T Cell Driven Immunotherapies: From CAR T and TILs to T Cell EngagersView all 4 articles
Non-signalling but all important: how the linker, hinge, and transmembrane domains in the CAR hold it all together
Provisionally accepted
Grace Bernard
Laura Evgin*- BC Cancer Research Institute, Faculty of Medicine, University of British Columbia, Vancouver, Canada
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The chimeric antigen receptor (CAR) is a synthetic and modular molecule composed of both signalling and non-signalling domains that allows a T cell to recognize cell surface antigens and trigger cytolytic functionality. It is appreciated that the non-signalling structural components, including the linker, hinge, and transmembrane domains, can dramatically alter how the CAR molecule interacts with itself and other endogenous molecules in the immune synapse. Herein, we describe the current understanding of how the structural domains can alter CAR T cell therapeutic efficacy and highlight how knowledge of the target antigen characteristics can inform CAR design choices.
Keywords: Chimeric antigen receptor (CAR T), T cell, Transmembrane domain (TMD), hinge domain, Linker region
Received: 11 Jul 2025; Accepted: 06 Oct 2025.
Copyright: © 2025 Bernard and Evgin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Laura Evgin, levgin@bcgsc.ca
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.