What are bispecific antibodies and what formats exist?

Bispecific antibodies (bsAbs) bind two different antigens simultaneously, enabling novel mechanisms. Formats include: 1) IgG-like - CrossMab, knobs-into-holes, DuoBody; retain Fc functions and half-life. 2) Fragment-based - BiTE (tandem scFv, small, short half-life), DART, diabodies; easier manufacturing but need half-life extension. 3) Asymmetric - different binding arms for distinct targets. 4) Appended - additional binding domains fused to IgG. Mechanisms: T-cell engagement (CD3 x tumor antigen, like blinatumomab for leukemia); dual pathway blocking (EGFR x MET); enhanced specificity (requiring two targets for activity); bridging (Factor IXa x X for hemophilia); and piggyback delivery across barriers. Manufacturing challenges include chain pairing (light chain/heavy chain mispairing) and expression balance. Over 100 bsAbs in clinical development.