Antibody Fusion Proteins: Applications in Brain Targeting

Advances in genetic engineering and expression systems have led to rapid progress in the development of antibodies fused to other proteins. These “antibody fusion proteins” combine the unique targeting ability of antibodies with the activity of the non-antibody partner. One promising application of these novel molecules is drug delivery to the brain, an organ difficult to target due to the presence of the blood-brain barrier (BBB), which effectively restricts transport from the blood of water soluble molecules larger than several hundred daltons. However, the tightly joined capillary endothelial cells, which form the BBB, have specific receptors that can be exploited by the antibody fusion proteins for transport from the blood to the brain. This can be achieved by fusing the antibody of interest to a protein with receptors on the BBB. An alternative approach is to fuse the protein of interest to an antibody specific for a BBB receptor. In both cases, antibody fusion proteins can either be the diagnostic and / or therapeutic agents themselves, or they can be used as universal vectors to deliver the desired active agent into the brain. During the last ten years multiple antibody fusion proteins have been developed for brain targeting and proof of principle has been established in animal models. The present review describes strategies for construction of antibody fusion proteins for brain targeting and discusses the in vitro and in vivo properties of these molecules.