Development of a Recombinant Monospecific Anti-PLGF Bivalent Nanobody and Evaluation of it in Angiogenesis Modulation

Nikooharf, Abolfazl; Arezumand, Roghaye; Mansouri, Kamran; Khoshi, Amirhosein; Ahmadabad, Hasan Namdar

doi:10.1007/s12033-020-00275-7

Cited by 11 publications

(9 citation statements)

References 30 publications

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“…Among studies in solid tumors, innovations such as self-luminescing BRET-FRET NIR-emitting nanoparticles have enabled in vivo mapping of lymphatic networks and small metastases [113]. Especially for studying difficult-to-access pathologies such as age-related macular degeneration [114] and diabetic retinopathy, biosensors can bring a substantial advantage for treatment decisions. Often, these pathologies are characterized by an inflammatory hypoxic environment that results in the upregulation of the HIF target VEGF and pathological neovascularization in the eye [115].…”

Section: Discussionmentioning

confidence: 99%

Ways into Understanding HIF Inhibition

Schönberger

Fandrey

Prost-Fingerle

2021

Cancers

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Hypoxia is a key characteristic of tumor tissue. Cancer cells adapt to low oxygen by activating hypoxia-inducible factors (HIFs), ensuring their survival and continued growth despite this hostile environment. Therefore, the inhibition of HIFs and their target genes is a promising and emerging field of cancer research. Several drug candidates target protein–protein interactions or transcription mechanisms of the HIF pathway in order to interfere with activation of this pathway, which is deregulated in a wide range of solid and liquid cancers. Although some inhibitors are already in clinical trials, open questions remain with respect to their modes of action. New imaging technologies using luminescent and fluorescent methods or nanobodies to complement widely used approaches such as chromatin immunoprecipitation may help to answer some of these questions. In this review, we aim to summarize current inhibitor classes targeting the HIF pathway and to provide an overview of in vitro and in vivo techniques that could improve the understanding of inhibitor mechanisms. Unravelling the distinct principles regarding how inhibitors work is an indispensable step for efficient clinical applications and safety of anticancer compounds.

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Section: Discussionmentioning

confidence: 99%

Ways into Understanding HIF Inhibition

Schönberger

Fandrey

Prost-Fingerle

2021

Cancers

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“…Nikooharf et al. ( 34 ) developed a bivalent anti-PLGF nanobody to test as suppressor of the angiogenesis progression and observed that it could inhibit cell proliferation, capillary-like structure formation and motility.…”

Section: Nanobody Applications In Cancer Researchmentioning

confidence: 99%

“…Several anti-spike/anti-RBD neutralizing antibodies have been isolated from both patients and by in vitro selection, some of them have entered clinical trials and cocktails of ligands binding to different epitopes have been proposed to overcome resistance due to the virus mutations ( 127 , 166 ). Multispecific antibody fragments are an alternative solution to prevent mutation-dependent resistance, as it has been already summarized in recent reviews ( 34 , 127 , 167 ). Since the research on anti-SARS-CoV-2 is particularly active and new publications appear constantly, here we report only those relevant to the subject of the present review and published in the first 2021 quarter.…”

Section: Nanobody Applications In Infectious Diseasesmentioning

confidence: 99%

Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment

et al. 2022

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Recombinant antibodies such as nanobodies are progressively demonstrating to be a valid alternative to conventional monoclonal antibodies also for clinical applications. Furthermore, they do not solely represent a substitute for monoclonal antibodies but their unique features allow expanding the applications of biotherapeutics and changes the pattern of disease treatment. Nanobodies possess the double advantage of being small and simple to engineer. This combination has promoted extremely diversified approaches to design nanobody-based constructs suitable for particular applications. Both the format geometry possibilities and the functionalization strategies have been widely explored to provide macromolecules with better efficacy with respect to single nanobodies or their combination. Nanobody multimers and nanobody-derived reagents were developed to image and contrast several cancer diseases and have shown their effectiveness in animal models. Their capacity to block more independent signaling pathways simultaneously is considered a critical advantage to avoid tumor resistance, whereas the mass of these multimeric compounds still remains significantly smaller than that of an IgG, enabling deeper penetration in solid tumors. When applied to CAR-T cell therapy, nanobodies can effectively improve the specificity by targeting multiple epitopes and consequently reduce the side effects. This represents a great potential in treating malignant lymphomas, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma and solid tumors. Apart from cancer treatment, multispecific drugs and imaging reagents built with nanobody blocks have demonstrated their value also for detecting and tackling neurodegenerative, autoimmune, metabolic, and infectious diseases and as antidotes for toxins. In particular, multi-paratopic nanobody-based constructs have been developed recently as drugs for passive immunization against SARS-CoV-2 with the goal of impairing variant survival due to resistance to antibodies targeting single epitopes. Given the enormous research activity in the field, it can be expected that more and more multimeric nanobody molecules will undergo late clinical trials in the next future.Systematic Review Registration

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“…PlGF-specific nanobodies with affinities in the nM range have been identified by phage-display and studied as monomers and dimers [139,140]. Their anti-angiogenic activity was demonstrated with several in vitro angiogenic assays.…”

Section: Antibodies and Antibody Fragmentsmentioning

confidence: 99%

A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics

Gaucher

Vidal

et al. 2021

Molecules

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The vascular endothelial growth factor (VEGF) family of cytokines plays a key role in vasculogenesis, angiogenesis, and lymphangiogenesis. VEGF-A is the main member of this family, alongside placental growth factor (PlGF), VEGF-B/C/D in mammals, and VEGF-E/F in other organisms. To study the activities of these growth factors under physiological and pathological conditions, resulting in therapeutic applications in cancer and age-related macular degeneration, blocking ligands have been developed. These have mostly been large biomolecules like antibodies. Ligands with high affinities, at least in the nanomolar range, and accurate structural data from X-ray crystallography and NMR spectroscopy have been described. They constitute the main focus of this overview, which evidences similarities and differences in their binding modes. For VEGF-A ligands, and to a limited extent also for PlGF, a transition is now observed towards developing smaller ligands like nanobodies and peptides. These include unnatural amino acids and chemical modifications for designed and improved properties, such as serum stability and greater affinity. However, this review also highlights the scarcity of such small molecular entities and the striking lack of small organic molecule ligands. It also shows the gap between the rather large array of ligands targeting VEGF-A and the general absence of ligands binding other VEGF members, besides some antibodies. Future developments in these directions are expected in the upcoming years, and the study of these growth factors and their promising therapeutic applications will be welcomed.

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Development of a Recombinant Monospecific Anti-PLGF Bivalent Nanobody and Evaluation of it in Angiogenesis Modulation

Cited by 11 publications

References 30 publications

Ways into Understanding HIF Inhibition

Ways into Understanding HIF Inhibition

Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment

A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics

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