 Abstract Chimeric Antigen Receptors, CARs, and Synthetic Notch, SYN Notch, receptors are engineered cell surface receptors that can be used to detect and respond to target antigens. To expand their targeting capabilities, researchers have developed universal receptor systems that can be programmed post-translationally using covalently attached antibodies. These antibodies contain a Benzylgonene, BG, motif that allows them to bind to a SNAP tag self-labeling enzyme, which then triggers the receptor's activation. The researchers demonstrated that this system could be used to target antigen-specific cars and SYN Notch receptors with clinically relevant antibodies, such as those against cancer cells. They also developed a mathematical model to better understand how the parameters affect the receptor's signaling. This new approach provides a powerful strategy to post-translationally reprogram the targeting specificity of engineered cells. This article was authored by Eliza Ruffo, Adam Abuchi, Yaniv Tyvan, and others.