Dual-affinity re-targeting proteins

Dual-affinity re-targeting proteins (DARTs) encompasses of two Fv fragments, containing two single antigen-binding sites formed when two Fv fragments heterodimerize. The Fv1 contains of a VH from antibody A and a VL from antibody B, whereas Fv2 contains VH from antibody B and VL from antibody A in the order of VL (1)-VH (2) and VL (2)-VH (1) (Fig. 1). This amalgamation permits DART to mimic natural interaction within an IgG molecule. Short linker sequences between the VL and VH segments encourage a posttranslational “diabody”-type association. The peptide linkers and the covalent linkage between the two DART chains limits the freedom of the antigen binding domains, resulting in a stable association between target and effector cells. DART can be synthesized in the mammalian expression systems. DART are more stable and potent. DART does not contain Fc region and, therefore it has a short serum half-life. Several DART antibodies are under development for T-cell redirection, modulation of receptor signaling and neutralization of viruses. DART molecules were found to be more consistent than BiTE molecules in targeting and killing B-cell lymphoma.

Formats of bispecific antibodies (BsAbs)