An extracellular, optogenetic antibody platform for stimulus-gated antigen recognition and modulation of cell behavior

Here, we present extrabody, an activatable, modular antibody platform that enables optogenetic or chemical reassembly of split antibody fragments for inducible extracellular antigen recognition. We demonstrate compatibility across diverse targets, including GFP, mCherry, and the tumor-associated antigens EGFR and HER2, and show that both nanobody- and scFv-derived fragments support light-dependent reconstitution. Extrabody enables input-gated cell-cell interactions and antigen transfer, providing external control over intercellular communication. Integration with synNotch receptors and chimeric antigen receptors (CARs) further allows dual-input regulation of downstream responses, including gene expression, cytokine release, and cytotoxicity. Together, these results establish extrabody as a versatile and generalizable interface for externally controlled cellular communication and synthetic signaling.