Benzylguanine-conjugated antibody adaptor (BG-Ab) (BG-Ab adaptor)

The Benzylguanine-conjugated antibody adaptor (BG-Ab) is a specialized molecular bridge used in modular chimeric antigen receptor (CAR) T-cell therapy, specifically the SNAP-CAR system. It consists of a targeting element, typically a monoclonal antibody or single-chain variable fragment (scFv), chemically linked to a benzylguanine (BG) moiety. This BG group acts as a substrate for the SNAP-tag, a modified human O6-alkylguanine-DNA alkyltransferase (AGT) expressed on the surface of universal CAR T-cells (Rodgers et al., 2016, PNAS). When the adaptor is introduced, it reacts covalently and irreversibly with the SNAP-tag, functionalizing the T-cell to recognize specific tumor antigens. This technology is designed to overcome the limitations of conventional CAR T-cells, such as fixed antigen specificity and lack of dose control. By switching or combining different BG-conjugated adaptors, clinicians can target multiple antigens simultaneously or sequentially to prevent tumor escape (Zajonc et al., 2021, Frontiers in Immunology). The system is primarily being developed for oncology applications, including both hematologic malignancies and solid tumors. The modularity of the BG-Ab adaptor allows for a "universal" T-cell product that can be redirected against any antigen for which a BG-conjugated binder exists. This approach also offers a safety switch, as the activity of the T-cells is dependent on the presence and concentration of the adaptor molecule.

Other names

SNAP-tag adaptorBG-antibodyBG-scFvUniversal CAR adaptorBenzylguanine-modified antibody

Covalent conjugation to the SNAP-tag receptor on CAR T-cells, enabling antigen-specific T-cell activation and cytotoxic activity against target cells.