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

The benzylguanine-conjugated antibody adaptor is a synthetic therapeutic component used in modular chimeric antigen receptor (CAR) T-cell systems, specifically the SNAP-CAR platform (Rodgers et al., 2016, PNAS). It consists of a targeting moiety, such as a monoclonal antibody or single-chain variable fragment (scFv), chemically conjugated to benzylguanine (BG) molecules. The BG moiety serves as a highly specific substrate for the SNAP-tag, a 20 kDa mutant of the human DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (MGMT) (Keppler et al., 2003, Nature Biotechnology). In practice, the adaptor binds to a specific tumor-associated antigen on the surface of a cancer cell, while the BG group reacts covalently and irreversibly with SNAP-tag receptors expressed on the surface of universal CAR-T cells. This interaction creates a stable bridge that recruits the T-cell to the tumor, leading to the formation of a synthetic immunological synapse and subsequent tumor cell lysis. This modular design allows for the targeting of multiple different antigens using a single universal CAR-T cell product by simply exchanging the adaptor molecule. Furthermore, the system provides a safety mechanism, as the activity of the CAR-T cells can be controlled or terminated by adjusting the administration or dosage of the BG-conjugated adaptor (Zajc et al., 2020, Nature Communications).

Other names

SNAP-tag adaptorBG-conjugated antibodySNAP-tag ligand-antibody conjugateBenzylguanine-modified scFvSNAP-CAR adaptor

The adaptor facilitates a covalent, irreversible bond between a SNAP-tag-expressing effector cell (such as a CAR-T cell) and a tumor cell by binding the tumor-associated antigen via its antibody domain and reacting with the SNAP-tag receptor via its benzylguanine moiety.