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Review
. 2021 Aug;385(2):445-456.
doi: 10.1007/s00441-021-03479-8. Epub 2021 Jun 16.

Nanobodies: new avenue to treat kidney disease

Nicola Wanner  1 , Thomas Eden  2 , Nastassia Liaukouskaya  3 , Friedrich Koch-Nolte  2
Affiliations
Review

Nanobodies: new avenue to treat kidney disease

Nicola Wanner et al. Cell Tissue Res. 2021 Aug.

Abstract

Current therapeutic options for renal diseases are limited, and the search for disease-specific treatments is ongoing. Nanobodies, single-domain antibodies with many advantages over conventional antibodies, provide flexible, easy-to-format biologicals with many possible applications. Here, we discuss the potential use of nanobodies for renal diseases.

Keywords: Conventional antibodies; Nanobodies; Renal diseases.

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Conflict of interest statement

F.K.-N. is a co-inventor on patent applications on CD38-specific and P2X7-specific nanobodies.

Figures

Fig. 1
Fig. 1
Structure, formats, and applications of VHHs. Conventional antibodies consist of two heavy and two light chains, and their antigen-binding region (paratope) is encoded by the variable domains of both chains (VH and VL). In case of camelid heavy chain antibodies, the antigen is recognized by the variable domain of the heavy chain (VHH) (A). Monomeric or dimeric (bivalent or biparatopic) nanobodies can be linked to the constant region (Fc) of any isotype to mediate different effector functions (e.g., complement dependent cytotoxicity (CDC) or antibody-dependent cellular cytotoxicity (ADCC)) (Schriewer et al. 2020) (B). VHHs can also be used as binding domains of chimeric antigen receptors (Nb-CAR) (Hambach et al. 2020) (C). Due to their modular structure, nanobodies can function as building blocks in multimeric constructs binding the same (multivalent) or different (multiparatopic) epitopes. The in vivo half-life of mono or multivalent nanobodies can be tuned, e.g., by genetic fusion to an albumin-specific nanobody (Tijink et al. 2008) (D). Monovalent VHHs can be conjugated chemically to radioisotopes (Huang et al. 2008) or fluorochromes (Fumey et al. 2017) and genetically to toxins (Mutter et al. 2018) and fluorescent proteins (Rothbauer et al. 2006) (E). Examples for nanobodies currently undergoing clinical trials include BCMA nanobody CAR T cells, Vobarilizumab, M1095, and Ozoralizumab, while Caplacizumab has already been FDA/EMA approved (F). scFv single-chain variable fragment, Ab antibody, hcAb heavy-chain antibody, ALB albumin, Nb nanobody, BCMA B cell maturation antigen, MM multiple myeloma, RA rheumatoid arthritis, SLE Systemic Lupus Erythematosus, SCP severe chronic psoriasis, TTP thrombotic thrombocytopenic purpura
Fig. 2
Fig. 2
Potential applications for nanobodies in kidney disease. PEG polyethylene glycol, PC plasma cell, CDC complement-dependent cytotoxicity, ADCC antibody-dependent cellular cytotoxicity
See this image and copyright information in PMC

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