O6-Benzylguanine-modified monoclonal antibody adaptor (BG-mAb)

The O6-Benzylguanine (BG) linker on monoclonal antibody adaptors is a synthetic component used in modular, 'switchable' immunotherapy platforms, most notably the SNAP-tag CAR T-cell system (Keppler et al., 2003, Nature Biotechnology). This technology utilizes a modified version of the human DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AGT), known as the SNAP-tag, which reacts rapidly and irreversibly with BG derivatives to form a stable thioether bond (Juillerat et al., 2019, Scientific Reports). In this therapeutic architecture, a monoclonal antibody is conjugated to a BG moiety to act as an intermediary adaptor; the antibody binds to a specific tumor antigen, while the BG linker serves as a docking site for effector cells, such as T cells engineered to express a SNAP-tag on their surface (Zajc et al., 2020, eLife). This modular design allows for precise control over the immune response, as the activity of the SNAP-CAR T cells is dependent on the administration and concentration of the BG-modified antibody adaptor. This approach aims to enhance the safety and versatility of cell therapies by allowing clinicians to titrate the dose to mitigate toxicities like cytokine release syndrome or to target multiple different antigens sequentially without the need for multiple CAR-T cell products.

Other names

Benzyl guanine linkerBG-adaptorSNAP-tag ligand-antibody conjugateO6-BG-modified antibodyBenzylguanine-conjugated antibody

Covalent conjugation of SNAP-tag-expressing effector cells to antibody-labeled tumor cells via an irreversible reaction between the SNAP-tag (a modified O6-alkylguanine-DNA alkyltransferase) and the O6-benzylguanine moiety.