Design strategies are particularlyneeded to avoid off-target toxicity when targeting PD-L1.24 To avoid nonspecific toxicity, two strategieswere employed in our study: (1) the design of a CAR based on a PD-L1-recognizingmonobody CAR with stronger affinity at a relatively lower pH typicalin the tumor microenvironment25 and (2)the integration with SynNotch recognizing a clinically validated tumor-associatedantigen (TAA) CD19 introduced into target cancer cells to form anIF THEN gate with PD-L1 for high precision control. The gene discussed is CD19; the disease is neoplasm.