Current Approaches and Future Perspectives for Nanobodies in Stroke Diagnostic and Therapy
Department of Neurology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Institute of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Author to whom correspondence should be addressed.
Antibodies 2019, 8(1), 5; https://doi.org/10.3390/antib8010005
Received: 30 November 2018 / Revised: 20 December 2018 / Accepted: 27 December 2018 / Published: 3 January 2019
(This article belongs to the Special Issue Nanobody)
Antibody-based biologics are the corner stone of modern immunomodulatory therapy. Though highly effective in dampening systemic inflammatory processes, their large size and Fc-fragment mediated effects hamper crossing of the blood brain barrier (BBB). Nanobodies (Nbs) are single domain antibodies derived from llama or shark heavy-chain antibodies and represent a new generation of biologics. Due to their small size, they display excellent tissue penetration capacities and can be easily modified to adjust their vivo half-life for short-term diagnostic or long-term therapeutic purposes or to facilitate crossing of the BBB. Furthermore, owing to their characteristic binding mode, they are capable of antagonizing receptors involved in immune signaling and of neutralizing proinflammatory mediators, such as cytokines. These qualities combined make Nbs well-suited for down-modulating neuroinflammatory processes that occur in the context of brain ischemia. In this review, we summarize recent findings on Nbs in preclinical stroke models and how they can be used as diagnostic and therapeutic reagents. We further provide a perspective on the design of innovative Nb-based treatment protocols to complement and improve stroke therapy.