An engineered T-cell engager with selectivity for high mesothelin-expressing cells and activity in the presence of soluble mesothelin

Mesothelin (MSLN) demonstrates the improved ability to distinguish between high MSLN-expressing tumors and normal tissue, even in the presence of soluble MSLN. In preclinical studies using human pancreatic cancer models, NM28-2746 showed potent T-cell activation and cytotoxicity against high MSLN-expressing cells, while being less effective against low MSLN-expressing cells. Additionally, when combined with the checkpoint inhibitor NM21-1480, NM28-2746 demonstrated significant tumor suppression and increased T-cell infiltration.