Biotin-LLE tag (Biotin-LLE)

The Biotin-LLE tag is a synthetic neo-epitope utilized in modular or switchable chimeric antigen receptor (CAR) T-cell therapy platforms (Ma et al., 2016, PNAS). In this system, the CAR-T cells are not designed to bind directly to tumor antigens; instead, they are engineered to recognize the Biotin-LLE tag, which is absent from the natural human proteome (Young et al., 2012, PNAS). This tag is conjugated to an adapter molecule, typically an antigen-binding fragment (Fab), which provides the specificity for a tumor-associated antigen such as CD19 or HER2 (US Patent 10,662,243). By separating the antigen recognition and T-cell activation components, this platform allows for precise control over the intensity and duration of the immune response through the titration of the adapter Fab (Cao et al., 2016, Angewandte Chemie). This approach aims to improve the safety profile of CAR-T therapies by providing a rheostat mechanism to manage toxicities like cytokine release syndrome and to prevent antigen escape by allowing the same CAR-T cells to target multiple antigens sequentially or simultaneously.

Other names

Biotinylated LLE peptide tagBiotin-LLE-Fab conjugateBiotin-LLE neo-epitopeBiotin-LLE adapter tag

The Biotin-LLE tag serves as a synthetic bridge in a switchable CAR-T (sCAR-T) system. The adapter Fab fragment binds to a specific tumor-associated antigen, while the anti-biotin CAR-T cell recognizes the Biotin-LLE tag on the adapter. This interaction facilitates the formation of a synthetic immune synapse, triggering T-cell signaling, cytokine release, and cytotoxic activity against the tumor cell.