Engineering broadly reactive human notch ligands as novel tools for biomedical applications

A method for activating Notch signaling in cells undergoing adoptive transfer, comprising contacting the cells with an engineered DLL4 protein;

• wherein the engineered DLL4 protein comprises a conservative amino acid substitution at a residue corresponding to residues 28, 107, 143, 194, and 206 as set forth in SEQ ID NO:
• 1 and further comprising at least one conservative amino acid substitution at residues 256, 257, 271, 280, 301, and 305 as set forth in SEQ ID NO:
• 1;
• and
• wherein the engineered DLL4 protein is anchored to a solid surface or substrate.