A major impediment to the development of immunotherapy has been the size of conventional antibodies because the antibody is often unable to reach its target.
In the late 1980’s, a single domain antibody comprising only of a VH domain was initially isolated by Greg Winter’s group at the MRC Laboratory of Molecular Biology in Cambridge, UK.
This single domain antibody was four times smaller than a Fab and half of the size of Fv.
Conventional antibodies are large (150 kDa), while small recombinant antibodies have a mass range between 25-50 kDa.
A sdAb is defined as the smallest antigen-binding fragment of antibodies, ranging from 11 to 15 kDa.
Single domain antibody, also known as domain antibody, VHH, VNAR or sdAb.
sdAb is an antibody fragment consisting of a single monomeric variable antibody domain and lacking the light chain and CH domain of the heavy chain in conventional Fab region.
It consists of a variable domain of an antibody VH or VL chain containing three or six naturally occurring complementary determining regions (CDRs) that permit specific recognition of the antigen.
In spite of this discovery in the late 1980’s, sdAb use was originally limited because single variable domains rarely retained the affinity of the parent antibody and were also poorly soluble and prone to aggregation.
The first single domain antibody was engineered from the VHH domain of heavy-chain antibody identified in camelids (e.g. dromedaries, camels, llamas, and alpacas).
These VHH domains display long surface loops, often larger than human antibodies and are able to penetrate cavities in target antigens.
The camelid heavy chain antibodies present advantages over common antibodies in the design, production, and application of clinically valuable reagents.
Given their high affinity and specificity, the small size of sdAbs makes them particularly suitable for targeting antigens in obstructed locations, such as tumors where penetration into poorly vascularized tissue is crucial to the success of the drug.
Singh Biotechnology has leveraged the fact that the single domain nature of these antibodies provides unique advantages that set them apart for research, diagnostic and therapeutic applications.