Abstract
Antibodies have become one of the most successful therapeutics for a number of oncology and inflammatory diseases. So far, central nervous system (CNS) indications have missed out on the antibody revolution, while they remain ‘hidden’ behind several hard to breach barriers. Among the various antibody modalities, single-domain antibodies (sdAbs) may hold the ‘key’ to unlocking the access of antibody therapies to CNS diseases. The unique structural features of sdAbs make them the smallest monomeric antibody fragments suitable for molecular targeting. These features are of particular importance when developing antibodies as modular building blocks for engineering CNS-targeting therapeutics and imaging agents. In this review, we first introduce the characteristic properties of sdAbs compared to traditional antibodies. We then present recent advances in the development of sdAbs as potential therapeutics across brain barriers, including their use for the delivery of biologics across the blood–brain and blood–cerebrospinal fluid (CSF) barriers, treatment of neurodegenerative diseases and molecular imaging of brain targets.
Highlights
This study demonstrated that single-domain antibodies (sdAbs) are advantageous as a central nervous system (CNS) therapeutic antibody modality developed for intracerebral or intrathecal administration
Anti-epidermal growth factor receptor (EGFR) sdAbs in monomer and pentamer formats showed to be suitable for molecular optical imaging of glioblastoma tumors due to their respective short half-lives of 40 min and 80 min, while the same sdAbs engineered into a bivalent format fused with human IgG Fc have better potential to be exploited for therapeutic applications due to their extended half-lives (12.5 h) and enhanced avidity [136]
SdAbs are proving to be a versatile format for designing blood–brain barrier (BBB) carriers that could be combined in various display linkages with therapeutic monoclonal antibodies and other therapeutic cargos
Summary
The concept of single-domain antibodies (sdAbs) originated in the 90’s, with the proof-of-concept experiments demonstrating sdAbs as bone fide antigen binding fragments [1], and the discovery of camelid [2] and shark [3] heavy chain-only antibodies (HCAbs). Human VH and VL domains are of interest because of their human nature, a property that presumably makes them less immunogenic in humans compared to camelid VH Hs or nurse shark VNAR s. Antibodies 2019, 8, 27 because of their human nature, a property that presumably makes them less immunogenic in humans compared to camelid VHHs or nurse shark VNARs. The desirable desirablebiophysical, biophysical,biochemical, biochemical, structural properties of sdAbs, from repertoires are generally well known, have been described several reviews [4–. The high and folding ideal imaging agents, e.g., against In this respect, stability and stability folding properties of properties of sdAbs provide flexibility for labeling reactions with optimal outcomes. Constructs as CNS diagnostics and therapeutics (see Section 1.3)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
