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Diabody and triabody structures were solved in collaboration with the group of Dr. R.L. Williams
Diabodies
The structure of a homodimeric diabody with a five amino acid linker between VH and VL domains confirms an earlier model in that the two antigen binding sites of the diabody molecule are located at opposite ends of the molecule at a distance of about 70Å apart and pointing away from each other.
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Flexibility of the two Fv heads in a diabody is likely to be reduced. Modelling suggested that a movement of the Fv heads of approximately 30o about a mean should be possible. Nevertheless, despite the reduced span between binding sites as well as reduced flexibility in comparison to IgG, bivalent diabodies show dramatically reduced dissociation rates (koff) as compared to the parental scFv molecules and have been shown to be attractive molecules molecules for in vivo imaging of tumours (see below).
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Triabodies
Shortening of the linker between VH and VL domains to < 1-2 AS promotes formation of a trimeric molecule. Below is the structure of such a triabody.
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The triabody structure may be used as a blueprint for the design and construction of trivalent and trispecific antibody fragments (e.g. by by linking the heavy and light chain V-domains of three different antibodies A , B and C to form two different chains VHA-VLB , VHB-VLC and VHC-VLA).
Triabodies could bind three different or identical epitopes on the same molecule leading to very high apparent affinities especially on antigen surfaces displaying repeated epitopes (analogously to IgM). The three fold symmetry may also be of advantage in neutralizing viruses as it could mimick the three fold symmetry common in many viral coat proteins.
Like diabodies, triabodies might be useful immunotherapeutic agents for the activation of resting T-cells by simultaneously crosslinking of both CD3 with CD28 on the T-cell and targeting the activated T-cell to a tumor antigen with its third specificity.
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Diabody Expression and Applications >
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