Fig. 2: Bispecific antibody constructs for CD3+ T-cell redirection.
From: Overcoming the challenges associated with CD3+ T-cell redirection in cancer
A typical IgG-like bispecific antibody (shown) consists of two heavy chains and two light chains, subdivided into variable domains and constant domains. The Fab region (antigen-binding domain) and Fc region (effector-function domain) are indicated. VH variable heavy, VL variable light, CH constant heavy, CL constant light. Various bispecific antibody formats exist for CD3+ T-cell redirection: bispecific T-cell engager (BiTE), BiTE-Fc; dual-affinity re-targeting (DART), DART-Fc; tetravalent DART; bispecific killer cell engager (BiKE); tri-specific killer cell engager (TriKE); single-chain variable fragment (scFv)-scFv-scFv; diabody; tandem diabody (TandAb); knobs-in-holes cognate light chains; knobs-in-holes common light chains; DuoBody; TrioMab; CrossMab Fab; CrossMab VH-VL; 2:1 CrossMab; 2:2 CrossMab; scFv-IgG; DVD-Ig; IgG-IgG; and Fab-scFv-Fc. DuoBody bispecific antibodies are formatted on an IgG1 backbone and are generated by controlled Fab arm exchange of complementary CH3 domain mutations that promote heterodimerisation (K409R refers to a lysine (K) to arginine (R) amino acid substitution; F405L refers to phenylalanine (F) to leucine (L) amino acid substitution).
