Generation of Bispecific and Tandem Diabodies

Conventionally, antibody phage display has been used to isolate recombinant antibodies that are monovalent in their interaction with target antigens. These antibodies can be reengineered for expression in mammalian cell culture as full-length, monospecific immunoglobulins. An emerging branch of research has sought to generate bivalent recombinant antibodies by manipulating the length of the linker separating heavy- and light-chain variable domains in single-chain Fv proteins, thereby promoting inter-scFv interaction and the formation of “diabodies.” With careful control, this can generate scFv-based proteins able to bind two very distinct targets, “bispecific diabodies.” Further manipulation enables the assembly of higher-order complexes.