Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 34 (1), 11-26

The Therapeutic Potential of Nanobodies

Affiliations
Review

The Therapeutic Potential of Nanobodies

Ivana Jovčevska et al. BioDrugs.

Abstract

Today, bio-medical efforts are entering the subcellular level, which is witnessed with the fast-developing fields of nanomedicine, nanodiagnostics and nanotherapy in conjunction with the implementation of nanoparticles for disease prevention, diagnosis, therapy and follow-up. Nanoparticles or nanocontainers offer advantages including high sensitivity, lower toxicity and improved safety-characteristics that are especially valued in the oncology field. Cancer cells develop and proliferate in complex microenvironments leading to heterogeneous diseases, often with a fatal outcome for the patient. Although antibody-based therapy is widely used in the clinical care of patients with solid tumours, its efficiency definitely needs improvement. Limitations of antibodies result mainly from their big size and poor penetration in solid tissues. Nanobodies are a novel and unique class of antigen-binding fragments, derived from naturally occurring heavy-chain-only antibodies present in the serum of camelids. Their superior properties such as small size, high stability, strong antigen-binding affinity, water solubility and natural origin make them suitable for development into next-generation biodrugs. Less than 30 years after the discovery of functional heavy-chain-only antibodies, the nanobody derivatives are already extensively used by the biotechnology research community. Moreover, a number of nanobodies are under clinical investigation for a wide spectrum of human diseases including inflammation, breast cancer, brain tumours, lung diseases and infectious diseases. Recently, caplacizumab, a bivalent nanobody, received approval from the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for treatment of patients with thrombotic thrombocytopenic purpura.

Conflict of interest statement

Ivana Jovčevska and Serge Muyldermans declare they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Graphical representation of different antibody structures. a Classical antibodies consist of two identical heavy (variable—VH and constant—CH1/2/3 domains) and two identical light (variable—VL and constant—CL domain) chains connected with disulfide bonds. The antigen-binding region (variable fragment—Fv) consists of VH and VL connected with a linker peptide or stabilized with a disulfide bond in the cases of single-chain variable fragment (scFv) and disulfide-stabilized variable fragment (dsFv), respectively. b Camelid heavy-chain antibodies consist of two identical heavy chains only (variable—VHH and constant—CH2/3 domains). The antigen-binding region consists of a single variable domain VHH or nanobody
Fig. 2
Fig. 2
Ribbon representation of a nanobody (pdb 1JTT). The framework regions are in grey, the hypervariable H1, H2 and H3 antigen binding loops are in yellow, orange and red, respectively

Similar articles

See all similar articles

Cited by 1 article

References

    1. Baylin SB, Ohm JE. Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addiction? Nat Rev Cancer. 2006;6(2):107–116. doi: 10.1038/nrc1799. - DOI - PubMed
    1. Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33(Suppl):245–254. doi: 10.1038/ng1089. - DOI - PubMed
    1. Jabir NR, Anwar K, Firoz CK, Oves M, Kamal MA, Tabrez S. An overview on the current status of cancer nanomedicines. Curr Med Res Opin. 2018;34(5):911–921. doi: 10.1080/03007995.2017.1421528. - DOI - PubMed
    1. Lammers T, Hennink WE, Storm G. Tumour-targeted nanomedicines: principles and practice. Br J Cancer. 2008;99(3):392–397. doi: 10.1038/sj.bjc.6604483. - DOI - PMC - PubMed
    1. Wang MD, Shin DM, Simons JW, Nie S. Nanotechnology for targeted cancer therapy. Expert Rev Anticancer Ther. 2007;7(6):833–837. doi: 10.1586/14737140.7.6.833. - DOI - PubMed
Feedback