Core Viewpoint - The research presents a breakthrough in T cell therapy by designing the world's first soluble Notch agonist, enabling efficient T cell differentiation in suspension culture and enhancing T cell function and anti-tumor immunity [3][7][8]. Group 1: Research Background - Notch signaling pathway is one of the most evolutionarily conserved pathways, crucial for the development and function of immune cells, particularly T cells [2][10]. - Traditional methods for T cell production rely on complex environments, making large-scale production challenging and costly [7][11]. Group 2: Research Breakthrough - The research team utilized AI protein design tools to create a soluble Notch agonist that activates the Notch signaling pathway in suspension culture, overcoming the mechanical activation challenge [3][8][12]. - The designed C3-DLL4 structure effectively bridges cells, facilitating the formation of immune synapses and activating Notch signaling [13][14]. Group 3: Applications and Advantages - The new method allows for the mass production of T cells in suspension bioreactors, significantly reducing production time and costs compared to traditional methods [16][19]. - In vivo experiments showed that C3-DLL4 enhances T cell function, indicating potential for developing Notch enhancers to improve cancer vaccines and infection prevention [18][19]. Group 4: Future Prospects - The research team is developing an upgraded version, C515H-DLL4, which further improves T cell differentiation efficiency, marking a step towards practical applications [22]. - The AI-designed proteins offer advantages in manufacturing, storage, and clinical administration, potentially transforming CAR-T cell production and vaccine development [23].