Nanobodies as modulators of inflammation: potential applications for acute brain injury.

Bjã¶Rn Rissiek,Friedrich Koch-Nolte,Tim Magnus

doi:10.3389/fncel.2014.00344

Bjã¶Rn Rissiek, Friedrich Koch-Nolte + Show 1 more

Open Access

https://doi.org/10.3389/fncel.2014.00344

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Abstract

Nanobodies are single domain antibodies derived from llama heavy-chain only antibodies (HCAbs). They represent a new generation of biologicals with unique properties: nanobodies show excellent tissue distribution, high temperature and pH stability, are easy to produce recombinantly and can readily be converted into different formats such as Fc-fusion proteins or hetero-dimers. Moreover, nanobodies have the unique ability to bind molecular clefts, such as the active site of enzymes, thereby interfering with the function of the target protein. Over the last decade, numerous nanobodies have been developed against proteins involved in inflammation with the aim to modulate their immune functions. Here, we give an overview about recently developed nanobodies that target immunological pathways linked to neuroinflammation. Furthermore, we highlight strategies to modify nanobodies so that they can overcome the blood brain barrier and serve as highly specific therapeutics for acute inflammatory brain injury.

Highlights

CELLULAR NEUROSCIENCENanobodies as modulators of inflammation: potential applications for acute brain injury
FROM LLAMA HEAVY-CHAIN-ONLY ANTIBODIES TO SINGLE DOMAIN NANOBODIES Mammalian immunoglobulins are composed of two heavy and two light chains which together form the antigen-binding paratope
Nanobodies are single domain antibodies derived from llama heavy-chain only antibodies (HCAbs)

Summary

CELLULAR NEUROSCIENCE

Nanobodies as modulators of inflammation: potential applications for acute brain injury. The heavy-chains of HCAbs are composed of the antigen-binding variable domain (VHH) followed by a hinge region and two constant domains (CH2 and CH3), whereas the CH1 domain known from conventional antibodies is missing (Figure 1A; Hamers-Casterman et al, 1993). Apart from their unusual architecture, HCAbs differ from conventional antibodies in their antigen recognition: VH and VL of conventional antibodies usually form a concave or flat shaped paratope suited for the binding of small molecules, peptides, or large antigens (Sundberg and Mariuzza, 2002; Blanc et al, 2009; Muyldermans, 2013).

Nanobodies as modulators of brain inflammation

Findings

CONCLUSIONS