Soluble Notch agonists drive T cell production

The Notch signalling pathway is essential for the development and differentiation of various cell types, including immune cells. Notch ligands can promote T cell differentiation, a key step in manufacturing T cells for therapeutic use. However, Notch activation typically requires direct cell–cell contact, and a physical ‘pulling’ force to activate the receptor, posing challenges for the design of soluble agonists. Now, writing in Cell, Mout et al. have designed a soluble Notch agonist that promotes cell–cell contact, activating receptor signalling. This agonist induced T cell differentiation from cell progenitors in vitro, and stimulated endogenous T cells when administered to mice.

doi: https://doi.org/10.1038/d41573-025-00143-6

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