A5039602090- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Biochemical and Structural Characterization
- Immunotherapy and Immune Responses
- Alzheimer's disease research and treatments
- Protein purification and stability
- T-cell and B-cell Immunology
- HER2/EGFR in Cancer Research
- Toxin Mechanisms and Immunotoxins
- Advanced Biosensing Techniques and Applications
- Venomous Animal Envenomation and Studies
- Nanoparticle-Based Drug Delivery
- Supramolecular Self-Assembly in Materials
- Nanoplatforms for cancer theranostics
- Transgenic Plants and Applications
- Lipid Membrane Structure and Behavior
- Viral Infectious Diseases and Gene Expression in Insects
- Radiopharmaceutical Chemistry and Applications
- Galectins and Cancer Biology
- Animal Diversity and Health Studies
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- Antifungal resistance and susceptibility
- Blood groups and transfusion
VIB-UGent Center for Inflammation Research
2022-2025
Vrije Universiteit Brussel
2016-2025
Vlaams Instituut voor Biotechnologie
2005-2024
VIB-VUB Center for Structural Biology
2011-2013
Nanobodies, single-domain antigen-binding fragments of camelid-specific heavy-chain only antibodies offer special advantages in therapy over classic antibody because their smaller size, robustness, and preference to target unique epitopes. A Nanobody differs from a human heavy chain variable domain about ten amino acids spread all its surface, four hallmark Nanobody-specific the framework-2 region (positions 42, 49, 50, 52), longer third loop (H3) folding this area. For therapeutic...
Nanobodies are recombinant, antigen-specific, single-domain, variable fragments of camelid heavy chain-only antibodies. The innate supremacy nanobodies as a renewable source affinity reagents, together with their high production yield in broad variety expression systems, minimal size, great stability, reversible refolding and outstanding solubility aqueous solutions, ability to specifically recognize unique epitopes subnanomolar affinity, have combined make them useful class biomolecules for...
Accurate determination of tumor human epidermal growth factor receptor 2 (HER2)-status in breast cancer patients is possible via noninvasive imaging, provided adequate tracers are used. In this study, we describe the generation a panel 38 nanobodies, small HER2-binding fragments that derived from heavy-chain-only antibodies raised an immunized dromedary. search lead compound, subset nanobodies was biochemically characterized depth and preclinically tested for use as imaging xenografted...
Nanobodies are the smallest fully functional antigen-binding antibody fragments possessing ideal properties as probes for molecular imaging. In this study we labeled anti-human epidermal growth factor receptor type 2 (HER2) Nanobody with (68)Ga via a 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) derivative and assessed its use HER2 iPET imaging.The 2Rs15dHis6 lead optimized current-good-manufacturing-practice grade analog 2Rs15d were conjugated...
RIT has become an attractive strategy in cancer treatment, but still faces important drawbacks due to poor tumor penetration and undesirable pharmacokinetics of the targeting vehicles.Smaller radiolabeled antibody fragments peptides feature highly specific target accumulation, resulting low accumulation healthy tissue, except for kidneys.Nanobodies are smallest (MW < 15 kDa) functional antigen-binding that derived from heavy chain-only camelid antibodies.Here, we show extend kidney retention...
The antigen-binding fragment of functional heavy chain antibodies (HCAbs) in camelids comprises a single domain, named the variable domain HCAbs (VHH). VHH harbors remarkable amino acid substitutions framework region-2 to generate an that functions absence light partner. provide more hydrophilic, hence soluble, character but decrease intrinsic stability domain. Here we investigate role additional hallmark dromedary VHHs, i.e. extra disulfide bond between first and third loops. After...
Nanobodies are a novel type of immunoglobulinlike, antigen-binding protein with beneficial pharmacologic and pharmacokinetic properties that ideally suited to targeting cellular antigens for molecular imaging or therapeutic purposes. However, because their camelid, nonhuman origin, the possible immunogenicity when used in clinic is concern. Here we present new strategy quickly generate humanized <b>Methods:</b> We genetically grafted loops NbCEA5, Nanobody specificity colon carcinoma marker...
Envenoming following scorpion sting is a common emergency in many parts of the world. Our aim was to ameliorate current 100-kDa horse plasma antivenom serum (PAS)-derived Fab'(2) more quickly reach highly diffusible toxins (7 kDa). We immunized dromedaries with from Androctonus australis hector (Aah) scorpions and cloned single-domain antibody fragments or nanobodies (15 kDa) their B cells. Nanobodies against AahI' toxin (with AahII most toxic compound venom) were retrieved libraries,...
Abstract To quantify and characterize the potentially toxic protein aggregates associated with neurodegenerative diseases, a high‐throughput assay based on measuring extent of aggregate‐induced Ca 2+ entry into individual lipid vesicles has been developed. This approach was implemented by tethering containing sensitive fluorescent dye to passivated surface changes in fluorescence as result membrane disruption using total internal reflection microscopy. Picomolar concentrations Aβ42 oligomers...
It is well established that, in addition to conventional Abs, camelids (such as Camelus dromedarius and Lama glama) possess unique homodimeric H chain Abs (HCAbs) devoid of L chains. The Ag-binding site these HCAbs consists a single variable domain, referred VHH. widely accepted that VHHs, with distinct framework-2 imprints evolved within the V(H) clan III-family 3, are exclusively present on HCAbs. In this study, we report finding leader signal sequence linked genes displaying high degree...
GAK (cyclin G-associated kinase) is a key regulator of clathrin-coated vesicle trafficking and plays central role during development. Additionally, due to the unusually high plasticity its catalytic domain, it frequent 'off-target' clinical kinase inhibitors associated with respiratory side effects these drugs. In present paper, we determined crystal structure domain alone in complex specific single-chain antibodies (nanobodies). constitutively active weakly associates solution. The apo...
Variable domains of camelid heavy-chain antibodies, commonly named nanobodies, have high biotechnological potential. In view their broad range applications in research, diagnostics and therapy, engineering stability is particular interest. One important aspect the improvement thermostability, because it can immediate effects on conformational stability, protease resistance aggregation propensity protein. We analyzed sequences thermostabilities 78 purified nanobody binders. From this data,...
Abstract Local delivery of amyloid beta oligomers from the tip a nanopipette, controlled over cell surface, has been used to deliver physiological picomolar oligomer concentrations primary astrocytes or neurons. Calcium influx was observed when as few 2000 were delivered surface. When dosing stopped intracellular calcium returned basal levels below. prevented by presence in pipette extracellular chaperone clusterin, which is known selectively bind oligomers, and specific nanobody beta. These...
Snake envenoming is a globally neglected public health problem. Antivenoms produced using animal hyperimmune plasma remain the standard therapy for snakebites. Although effective against systemic effects, conventional antivenoms have limited efficacy local tissue damage. In addition, potential hypersensitivity reactions, high costs maintenance, and difficulties in homogeneity from batch-to-batch, are some of factors that motivated search innovative improved therapeutic products such...
While immunotherapy has revolutionized the oncology field, variations in therapy responsiveness limit broad applicability of these therapies. Diagnostic imaging immune cell, and specifically CD8+ T dynamics could allow early patient stratification result improved efficacy safety. In this study, we report development a nanobody-based immunotracer for non-invasive SPECT PET human T-cell dynamics. Nanobodies targeting CD8β were generated by llama immunizations subsequent biopanning. The lead...
Fluorescence molecular imaging plays a vital role in image-guided surgery. In this context, the urokinase plasminogen activator receptor (uPAR) is an interesting biomarker enabling detection and delineation of various tumor types due to its elevated expression on both cells microenvironment. study, anti-uPAR Nanobodies (Nbs) are generated through llama immunization with human murine uPAR protein. Extensive vitro characterization vivo testing radiolabeled variants conducted assess their...
Scorpion venom, containing highly toxic, small polypeptides that diffuse rapidly within the patient, causes serious medical problems. Nanobodies, single-domain antigen-binding fragments derived from dromedary heavy-chain antibodies, have a size closely matches of scorpion toxins. Therefore these nanobodies might be developed into potent immunotherapeutics to treat envenoming. Multiple sub-nanomolar affinity AahII, most toxic polypeptide Androctonus australis hector were isolated immunized...
Abstract γ‐Secretases are a family of intramembrane cleaving aspartyl proteases and important drug targets in Alzheimer's disease. Here, we generated mice deficient for all γ‐secretases the pyramidal neurons postnatal forebrain by deleting three anterior pharynx defective 1 ( Aph1 ) subunits Aph1abc cKO Cre + ). The show progressive cortical atrophy, neuronal loss, gliosis. Interestingly, this is associated with more than 10‐fold accumulation membrane‐bound fragments App, Aplp1, Nrg1, Dcc,...