Tandem scFvs are a class of bispecific antibody fragments. Two or more moieties of scFv string together to form tandem scFv, which has 1+1 (+1…) antigen-binding. scFvs are fused by a helical linker or a flexible linker. The format of tandem scFvs can be defined by the orientation of the VH and VL domain in the two individual scFvs (i.e., VL-VH or VH-VL) and the connecting linker. Without Fc domain, the smaller size of tandem scFv gives it a short half-life. Meanwhile, it also ensures a closer proximity to two or more targets.
The format of tandem scFvs has been extensively used in cancer immunotherapy. Among the class of BsAbs, BiTEs (bispecific T-cell engagers) are most famous. BiTEs comprise an anti-CD3 scFv and an anti-TAA scFv. They can retarget T cells to tumor-associated cells.