Diabodies có khả năng miễn dịch ít hơn BsAb quadroma có nguồn gốc từ và có thể dễ dàng sản xuất trong vi khuẩn trong năng suất cao (14). Diabodies Bispecific xuất hiện có hiệu quả hơn hơn BsAb quadroma có nguồn gốc từ trung gian tế bào T (11,12) và NK tế bào (15) độc tế bào trong ống nghiệm | 318 Kipriyanov Fig. 1. Schematic representation of the domain structure of immunoglobulin G Fab and scFv molecules. The scFv linker and Ag-binding sites are indicated L and Ag respectively . connected by a short linker to the VL domain of another Ab 7 11 12 Fig. 2B . The two antigen Ag -binding domains have been shown by crystallographic analysis to be on opposite sides of the diabody molecule so that they are able to crosslink two cells 13 Fig. 2C . Diabodies are potentially less immunogenic than quadroma-derived BsAb and can be easily produced in bacteria in high yields 14 . Bispecific diabodies appeared to be more effective than quadroma-derived BsAb in mediating T-cell 11 12 and NK-cell 15 cytotoxicity in vitro against tumor cells. In vivo the antitumor activity of diabodies was similar to that of the parental BsAbs which have longer blood retention because of their much larger size 15 16 . However the co-secretion of two hybrid scFvs may give rise to two types of dimer active heterodimers and inactive homodimers. A second problem is that the two chains of diabodies are held together by noncovalent associations of the VH and VL domains and can diffuse away from one another. Moreover to ensure the assembly of a functional diabody both hybrid scFvs must be expressed in the same cell in similar amounts. This latter requirement is difficult to uphold in eukaryotic expression systems such as yeast which are often preferred because high yields of enriched product can be obtained 17 18 . In contrast to native Abs diabodies have only one binding domain for each specificity. However bivalent binding is an important means of increasing the functional affinity and possibly the selectivity for particular cell types carrying densely clustered Ags. To circumvent the drawbacks of diabodies and to increase the valence stability and therapeutic potential of recombinant BsAbs we have recently Bispecific and Tandab Generation 319 Fig. 2. Schematic representation of bacterial .
