2025-11-03 スイス連邦工科大学ローザンヌ校(EPFL)
CAR T-cells attack cancer cell ©iStock photos (Nemes Laszlo)
<関連情報>
- https://actu.epfl.ch/news/custom-designed-receptors-boost-cancer-fighting-t/
- https://www.nature.com/articles/s41551-025-01532-3
強化された癌T細胞療法のためのプログラム可能なシグナル伝達活性を有する合成受容体の計算設計 Computational design of synthetic receptors with programmable signalling activity for enhanced cancer T cell therapy
Jan A. Rath,Lucas S. P. Rudden,Nazila Nouraee,Tiffany X. Y. Que,Christine Von Gunten,Cynthia Perez,Flora Birch,Yashashvi Bhugowon,Andreas Fueglistaler,Aisima Chatzi Souleiman,Patrick Barth & Caroline Arber
Nature Biomedical Engineering Published:28 October 2025
DOI:https://doi.org/10.1038/s41551-025-01532-3
Abstract
The tumour microenvironment (TME) plays a key role in tumour progression, and soluble and cellular TME components can limit CAR-T cell function and persistence. Targeting soluble TME factors to enhance anti-tumour responses of engineered T cells through chimeric receptors is not broadly explored owing to the unpredictable signalling characteristics of synthetic protein receptors. Here we develop a computational protein design platform for the de novo bottom-up assembly of allosteric receptors with programmable input–output behaviours that respond to soluble TME factors with co-stimulation and cytokine signals in T cells, called TME-sensing switch receptor for enhanced response to tumours (T-SenSER). We develop two sets of T-SenSERs targeting vascular endothelial growth factor (VEGF) or colony-stimulating factor 1 (CSF1) that are both selectively enriched in a variety of tumours. Combination of CAR and T-SenSER in human T cells enhances anti-tumour responses in models of lung cancer and multiple myeloma, in a VEGF- or CSF1-dependent manner. Our study sets the stage for the accelerated development of synthetic biosensors with custom-built sensing and responses for basic and translational cell engineering applications.
