Nanobodies: Next Generation of Cancer Diagnostics and Therapeutics

Yang, Emily; Shah, Khalid

doi:10.3389/fonc.2020.01182

Cited by 184 publications

(135 citation statements)

References 222 publications

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“…Finally, addition of any enzymatic domain to the small tag binders would allow the specific modification of the tagged POI, as it was elegantly shown with a minimal Rho kinase domain fused to the GFP nanobody to phosphorylate a GFP-tagged protein in Drosophila melanogaster ( Roubinet et al, 2017 ) or with a proximity-directed O-GlcNAcetylation linking the O-GlcNAc transferase activity to the GFP or EPEA nanobody in cell culture ( Ramirez et al, 2020 ). Several recent reviews have highlighted the versatility of the nanobodies for numerous applications both in clinical and biological research ( Beghein and Gettemans, 2017 ; Cheloha et al, 2020 ; Ingram et al, 2018 ; Muyldermans, 2020 ; Schumacher et al, 2018 ; Yang and Shah, 2020 ). The various functionalization strategies can be extended to these small tag binders.…”

Section: Discussionmentioning

confidence: 99%

Protein manipulation using single copies of short peptide tags in cultured cells and in Drosophila melanogaster

et al. 2021

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Cellular development and function rely on highly dynamic molecular interactions among proteins distributed in all cell compartments. Analysis of these interactions has been one of the main topics in cellular and developmental research and has been mostly achieved by the manipulation of proteins of interest (POIs) at the genetic level. Although genetic strategies significantly contributed to our current understanding, targeting specific interactions of POIs in a time- and space-controlled manner or analyzing the role of POIs in dynamic cellular processes such as cell migration or cell division would profit from more direct approaches. The recent development of specific protein binders, which can be expressed and function intracellularly, along with advancement in synthetic biology, have contributed to the creation of a new toolbox for direct protein manipulations. Here, we selected a number of short tag epitopes for which protein binders from different scaffolds have been generated and showed that single copies of these tags allowed efficient POIs binding and manipulation in living cells. Using Drosophila, we also find that single short tags can be utilized for POI manipulation in vivo.

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Section: Discussionmentioning

confidence: 99%

Protein manipulation using single copies of short peptide tags in cultured cells and in Drosophila melanogaster

et al. 2021

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“…Nbs are widely used for the direct detection of cancer cells ( Figure 1 and Figure 2 ). Currently, the most advanced Nb probe target is represented by the human epidermal growth factor receptor type 2 (HER2), a member of HER-kinase family, over-expressed by a variety of tumor types, including breast, ovarian, prostate and colorectal cancer [ 75 ]. In 2016, a phase I clinical trial demonstrated that a 68 Ga-HER2 Nbs 2Rs15d was able to detect primary tumor and distant metastases in breast cancer patients already 60 min post-injection, without any adverse effects [ 76 , 77 ].…”

Section: Nanobodies As Imaging Toolsmentioning

confidence: 99%

Nanobodies as Versatile Tool for Multiscale Imaging Modalities

et al. 2020

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Molecular imaging is constantly growing in different areas of preclinical biomedical research. Several imaging methods have been developed and are continuously updated for both in vivo and in vitro applications, in order to increase the information about the structure, localization and function of molecules involved in physiology and disease. Along with these progresses, there is a continuous need for improving labeling strategies. In the last decades, the single domain antigen-binding fragments nanobodies (Nbs) emerged as important molecular imaging probes. Indeed, their small size (~15 kDa), high stability, affinity and modularity represent desirable features for imaging applications, providing higher tissue penetration, rapid targeting, increased spatial resolution and fast clearance. Accordingly, several Nb-based probes have been generated and applied to a variety of imaging modalities, ranging from in vivo and in vitro preclinical imaging to super-resolution microscopy. In this review, we will provide an overview of the state-of-the-art regarding the use of Nbs in several imaging modalities, underlining their extreme versatility and their enormous potential in targeting molecules and cells of interest in both preclinical and clinical studies.

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“…Two non-covalently bound polypeptide chains were therefore used as an alternative [ 117 ]. Nanobodies are single-domain antibody fragments consisting of heavy-chain-only variable regions of antibodies, which have affinities similar to scFvs, but are less prone to misfolding [ 118 , 119 ]. Other than antibody-derived binding domains can be used as well.…”

Section: Chimeric Antigen Receptor-based Adoptive Immunotherapymentioning

confidence: 99%

Current Immunotherapy Approaches in Non-Hodgkin Lymphomas

et al. 2020

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Non-Hodgkin lymphomas (NHLs) are lymphoid malignancies of B- or T-cell origin. Despite great advances in treatment options and significant improvement of survival parameters, a large part of NHL patients either present with a chemotherapy-refractory disease or experience lymphoma relapse. Chemotherapy-based salvage therapy of relapsed/refractory NHL is, however, capable of re-inducing long-term remissions only in a minority of patients. Immunotherapy-based approaches, including bispecific antibodies, immune checkpoint inhibitors and genetically engineered T-cells carrying chimeric antigen receptors, single-agent or in combination with therapeutic monoclonal antibodies, immunomodulatory agents, chemotherapy or targeted agents demonstrated unprecedented clinical activity in heavily-pretreated patients with NHL, including chemotherapy-refractory cases with complex karyotype changes and other adverse prognostic factors. In this review, we recapitulate currently used immunotherapy modalities in NHL and discuss future perspectives of combinatorial immunotherapy strategies, including patient-tailored approaches.

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Nanobodies: Next Generation of Cancer Diagnostics and Therapeutics

Cited by 184 publications

References 222 publications

Protein manipulation using single copies of short peptide tags in cultured cells and in Drosophila melanogaster

Protein manipulation using single copies of short peptide tags in cultured cells and in Drosophila melanogaster

Nanobodies as Versatile Tool for Multiscale Imaging Modalities

Current Immunotherapy Approaches in Non-Hodgkin Lymphomas

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