Fig. 2

Schematics of a recombinant CAR-T cell. a Construct comprises a downstream signaling domain for T-cell activation; a co-stimulatory domain that enhances cytokine production; transmembrane domain traversing the cellular membrane for anchoring the CAR; spacer region affecting the flexibility and functionality; scFv: a targeting domain recognizes the tumor-associated antigen. b Schematics for a conditionally active biologics instilling “AND” logic gate characteristics to the CAR-T cell are shown. A pH-dependent scFv is engineered for binding to its cognate receptor on tumor cells with high affinity only within TME at pH < 7.4, i.e. “CAR-On” mode. In the context of antigens expressed on healthy cells (at pH 7.4) the affinity to cognate antigens is severely diminished i.e. “CAR-Off” mode thus sparing the normal/healthy cells