Camelid single-domain antibodies: A versatile tool for in vivo imaging of extracellular and intracellular brain targets

Li, Tengfei; Vandesquille, Matthias; Koukouli, Fani; Dudeffant, Clémence; Youssef, Ihsen; Lenormand, Pascal; Ganneau, Christelle; Maskos, Uwe; Czech, Christian; Grueninger, Fiona; Duyckaerts, Charles; Dhénain, Marc; Bay, Sylvie; Delatour, Benoı̂t; Lafaye, Pierre

doi:10.1016/j.jconrel.2016.09.019

Cited by 97 publications

(113 citation statements)

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“…Antibody fragments should be more specific and, if they can be delivered to the brain in sufficient amounts for PET detection, may allow documenting the epitope profile of the individual that could result in a more personalized immunotherapy, targeting those specific epitopes. Promising findings have been reported on this approach by us and others, supporting its further development [11,67]. …”

Section: Future Directionsmentioning

confidence: 63%

“…This latter experiment highlighted as well that humanization can dramatically alter the efficacy of the antibody, and that such antibodies should therefore be carefully studied before clinical trials to make sure that they will act as intended. We are not aware of other studies examining this for therapeutic tau antibodies but a report on single domain llama anti-tau antibody fragment as an imaging probe revealed a basic IEP (pI 9.5–10) for their diagnostic candidate [67]. It is likely that the potential effects of charge on neuronal uptake depends on the size of the molecule (antibody vs. fragment).…”

Section: How Does It Work?mentioning

confidence: 99%

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Tau Immunotherapies for Alzheimer’s Disease and Related Tauopathies: Progress and Potential Pitfalls1

Sigurdsson

2018

JAD

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Tau immunotherapies have now advanced from proof-of-concept studies to Phase 2 clinical trials. This review briefly outlines developments in the field and discusses how these therapies may work, which involves multiple variables that are connected in complex ways. These various factors are likely to define therapeutic success in humans and have not been thoroughly investigated, at least based on published reports.

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Section: Future Directionsmentioning

confidence: 63%

Section: How Does It Work?mentioning

confidence: 99%

Tau Immunotherapies for Alzheimer’s Disease and Related Tauopathies: Progress and Potential Pitfalls1

Sigurdsson

2018

JAD

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“…VHHs have been shown to recognize a wide range of epitope types, from small haptens [16,19] to the binding sites of enzymes [17,20], and can bind epitopes that cannot be recognized by conventional antibodies [21]. -The small size and basic isolectric point of VHHs allows them to penetrate tissues, pass through barriers, such as the blood-brain barrier [22][23][24][25][26], and bind intracellular antigens. -VHHs can be efficiently functionalized [27][28][29] and are widely used for imaging [24,26,30].…”

Section: Unique Properties Of Vhh Fragments and Their Use In Biotechnmentioning

confidence: 99%

Use of camel single-domain antibodies for the diagnosis and treatment of zoonotic diseases

Lafaye

2018

Comparative Immunology, Microbiology and Infectious Diseases

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A B S T R A C TCamelids produce both conventional heterotetrameric antibodies and homodimeric heavy-chain only antibodies. The antigen-binding region of such homodimeric heavy-chain only antibodies consists of one single domain, called VHH. VHHs provide many advantages over conventional full-sized antibodies and currently used antibody-based fragments (Fab, scFv), including high specificity, stability and solubility, and small size, allowing them to recognize unusual antigenic sites and deeply penetrate tissues. Since their discovery, VHHs have been used extensively in diagnostics and therapy. In recent decades, the number of outbreaks of diseases transmissible from animals to humans has been on the rise. In this review, we evaluate the status of VHHs as diagnostic and therapeutic biomolecular agents for the detection and treatment of zoonotic diseases, such as bacterial, parasitic, and viral zoonosis. VHHs show great adaptability to inhibit or neutralize pathogenic agents for the creation of multifunctional VHH-based diagnostic and therapeutic molecules against zoonotic diseases.

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“…Although V HH s do not originate from humans, the humanizations strategies of V HH s have successfully been undertaken by designing a humanized scaffold region onto the antigen-binding loops (CDRs) of specific V HH s can be grafted [100]. In addition, non-humanized and humanized V HH s with therapeutic potential have been applied in multiple areas, including hematology [101], inflammatory diseases [102], infectious diseases [103], in vivo imaging [104], neurological disorders [105] and oncology [106,107].…”

Section: Hh Heavy-chain Domain In Camelidsmentioning

confidence: 99%

The Development of Single Domain Antibodies for Diagnostic and Therapeutic Applications

Leow¹,

Cheng²,

Fischer³

et al. 2018

Antibody Engineering

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Monoclonal antibodies have become increasingly accepted as diagnostics and therapeutics for various human diseases due to their high affinity and specificity. However, several practical drawbacks are apparent for the reagents based on conventional IgG antibodies. With the emergence of antibody engineering, many problems were overcome when the recombinant antibody fragments such as Fabs, scFvs, diabodies and single domain antibodies (sdAbs), are developed. These fragments not only retain the specificity of the whole monoclonal antibodies, but are also easy to express and produce in prokaryotic expression systems. Rather unexpectedly, the natural sdAbs namely V HH s, V NAR s and variable lymphocyte receptors (VLRs) that comprise excellent biological activities were recently discovered in camelids, cartilaginous fish and lampreys, respectively. Due to their unique characteristics, including small size, high thermostability, stable folding in the nucleus and cytosol and long CDR3 regions which have access to cavities or clefts on the surface of proteins, these new binders are now investigated extensively as a substitute for conventional antibodies. This review describes the potential of sdAbs selected using in vitro display systems and their use in multiple applications.(polyclonal Abs) are heterogeneous antibody mixtures that are derived from multiple plasma cell lines. Because polyclonal antibodies comprise a mixture of different antibodies carrying numerous paratopes, they have excellent properties for recognizing antigens [2]. A monoclonal antibody (mAb) is a homogeneous antibody generated from a single B lymphocyte clone. Antibodies produced in mAb format have an extremely high specificity against a single epitope on antigens [3]. Recombinant antibodies (rAbs) are antibodies generated using molecular biology techniques. They are aimed to improve the sensitivity, selectivity, stability and immobilization properties in diagnostic applications, for example, in biosensors [4]. In making decision to use or generate polyclonal, monoclonal or recombinant antibodies, several factors should be considered, including commercial availability, possibility to raise animals, types of applications, time length of a project and costs [1]. Although a vast number of rAbs has been proposed [5][6][7][8], the natural sdAb fragments that were recently discovered from camelids (V HH s), sharks (V NAR s) and lampreys (VLRs) have shown to possess extraordinary features that are not found in conventional antibodies, such as a small dimension, an elevated stability and the capability of recognizing cavities and clefts on the surface of proteins that cannot be reached by conventional recombinant antibodies [9][10][11]. This chapter will discuss the availability of new binders derived from vertebrates and give an overview of their applications in a biomedical platform by recognizing specified targets from various diseases. Monoclonal antibodies and their limitationsThe first description of monoclonal antibody (mAbs) production was published ...

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Camelid single-domain antibodies: A versatile tool for in vivo imaging of extracellular and intracellular brain targets

Cited by 97 publications

References 58 publications

Tau Immunotherapies for Alzheimer’s Disease and Related Tauopathies: Progress and Potential Pitfalls1

Tau Immunotherapies for Alzheimer’s Disease and Related Tauopathies: Progress and Potential Pitfalls1

Use of camel single-domain antibodies for the diagnosis and treatment of zoonotic diseases

The Development of Single Domain Antibodies for Diagnostic and Therapeutic Applications

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