The DROP-CAR’s remote-control: (IMAGE)
Caption
The DROP-CAR’s remote-control: The signaling component of the chimeric antigen-receptor (CAR) inside the cell is linked to a strip of protein (S-chain) on the outside of the cell by a transmembrane domain (TM). The S-chain carries at its tip a computationally designed human domain known as dmLD3 that binds a protein named BCL-2. The cancer antigen-binding antibody of the CAR (its R domain) carries at its tail end the bit of BCL-2 recognized by dmLD3. Held together by this spontaneous protein-protein interaction, the CAR remains intact and functional until venetoclax disrupts that interaction. At that point, the dmLD3 and BCL-2 domains disengage and the CAR falls apart, switching off the CAR-T cell. When venetoclax is withdrawn, the CAR reassembles and the CAR-T cells get back to killing cancer cells.
Credit
Ludwig Cancer Research
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