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Mimicking the TCR immune synapse for improved CAR-T cell function

Tom Enbar¹ , Li Tang^1,2,*

¹Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
²Institute of Materials Science & Engineering, EPFL, Lausanne, Switzerland
* Correspondence: Li Tang(li.tang@epfl.ch)

In a recent paper published in Immunity, Xu and colleagues demonstrate that enhancing chimeric antigen receptor (CAR) clustering via liquid-liquid phase separation, particularly through the inclusion of CD3ε, improves immunological synapse (IS) formation, antigen sensitivity, and long-term cytotoxicity. Their optimized CAR design (EB6I28Z) mimics key features of TCR-based IS, reducing exhaustion and improving responses against both hematological and solid tumors.

https://doi.org/10.1038/s41422-025-01086-8

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