Members
Gholamreza Hassanzadeh Ghassabeh
Name of the laboratory
- VIB NANOBODY® VHH Core
- Vlaams Instituut voor Biotechnologie
- Pleinlaan 2
- 1050 Brussel, Belgium
- +32 (0)2 629 1801
Members of the laboratory
- Unit Leader
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Gholamreza Hassanzadeh Ghassabeh reza.hassanzadeh@vib.be
- Post-doc / Project manager
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Steve Schoonooghe steve.schoonooghe@vib.be
- Lab Coordinator
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Ema Romão ema.romao@vib.be
- Technicians
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Rolando Paciello rolando.paciello@vib.be
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Jelle Elseviers jelle.elseviers@vub.vib.be
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Jan Van Gompel Jan.VanGompel@vib.be
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Ana Rita Coelho Gomes rita.gomes@vib.be
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Isabelle Degors isabelle.degors@vib.be
Laboratory activity
Camelids were found to have IgGs (IgG2 & IgG3) in their serum devoid of light chains. When the antigen binding VHH domain (Trademarked as NANOBODY® by Ablynx N.V.) is isolated from these heavy-chain-antibodies, a 15 kDa single domain antigen binding fragment is obtained. Besides a near limitless repertoire diversity and the potential for highly discriminating (1 AA difference) & high affinity single domains, the absence of a VL (and a linker to make a scFv) has a number of marked advantages: easy identification, high stability, high solubility and a generally high expression yield. On top of that VHHs sometimes provide access to cryptic antigens & epitopes.
These characteristics make VHHs very flexible molecules useful in a wide variety of fields, such as immunotherapy, immunohistochemistry, immunomodulation, intracellular expression (intrabodies), bio-imaging and biosensor-applications. As proteomics tools, they can be deployed for expression profiling, physical mapping of proteins, protein-protein interaction studies, functional analysis and (in)activation of genes. Reformatting for these applications is easy: affinity tags, biotynilation, bivalent or bispecific constructs are all possible. They can even be re-formatted as an antibody in front of a human or mouse Fc if a ‘classic’ antibody format is required.
The VIB NANOBODY® VHH Core provides acces to the powerful VHH technology for both academic as non-academic researchers. At the VIB NANOBODY® VHH Core we try to cater to our clients with a customized service as much as possible by providing the following services:
- VHH generation
- VHH and antibody characterization
- VHH and antibody construct engineering
Research activities
Cancer Immunotherapy
We have close ties to VIB research groups studying and combating cancer. As such we have built up a strong expertise in cancer immunotherapy. From this knowledge we are developing VHH based therapeutic molecules for the diagnosis and treatment of cancer. This can be through attaching toxic payloads to cancer targeting VHHs and/or by making VHHs that identify (diagnosis) or target (therapeutics) immune cells important in the progression or destruction of tumors.
Serum half-life extension of therapeutics
Smaller sized therapeutic proteins with a size below the renal cut-off value (+/- 60 kDa) are rapidly cleared from circulation. This can be prevented in several ways. Two of the most common methods are by either making the molecule larger or through the addition of an affinity for an abundant molecule in serum. The first approach, mostly done through fusion to an Fc-domain is something we already have on offer. For the second approach, resulting in a smaller molecule with better tissue penetration and arguably less side-effects, we have been developing a set of VHHs that serve to extend the serum-half life of therapeutic proteins (mostly VHHs) in different species. We seek to characterize these VHHs as much as possible so they can be easily translated to a clinical setting. Currently we have an extensively characterized VHH available against human, mouse, cyno and rat albumin which we offer through licensing. Other VHHs for albumins in other species are also being actively persued.
Techniques available
- VHH generation
- Various immunization techniques
- Antibody phage library generation and screening
- Screening and affinity characterisation through ELISA, FACS, BLI(Octet), SPR(Biacore)
- Thermo-, solvent- and freeze-thaw stability determinations using fluorometric assays and Uncle platform
- In silico analysis of VHH B-cell lineages and potential developability issues
- (Re-)Engineering of VHH & Antibody constructs: Fc-fusions, GFP fusions, multi-specifics, multi-valents,...
Publications (2019-present)
- NMR-Based Analysis of Nanobodies to SARS-CoV-2 Nsp9 Reveals a Possible Antiviral Strategy Against COVID-19. Esposito G, Hunashal Y, Percipalle M, Venit T, Dieng MM, Fogolari F, Hassanzadeh G, Piano F, Gunsalus KC, Idaghdour Y, Percipalle P. Adv Biol (Weinh). 2021 Dec;5(12):e2101113
- An affinity-enhanced, broadly neutralizing heavy chain-only antibody protects against SARS-CoV-2 infection in animal models. Schepens B, van Schie L, Nerinckx W, Roose K, Van Breedam W, Fijalkowska D, Devos S, Weyts W, De Cae S, Vanmarcke S, Lonigro C, Eeckhaut H, Van Herpe D, Borloo J, Oliveira AF, Catani JPP, Creytens S, De Vlieger D, Michielsen G, Marchan JCZ, Moschonas GD, Rossey I, Sedeyn K, Van Hecke A, Zhang X, Langendries L, Jacobs S, Ter Horst S, Seldeslachts L, Liesenborghs L, Boudewijns R, Thibaut HJ, Dallmeier K, Velde GV, Weynand B, Beer J, Schnepf D, Ohnemus A, Remory I, Foo CS, Abdelnabi R, Maes P, Kaptein SJF, Rocha-Pereira J, Jochmans D, Delang L, Peelman F, Staeheli P, Schwemmle M, Devoogdt N, Tersago D, Germani M, Heads J, Henry A, Popplewell A, Ellis M, Brady K, Turner A, Dombrecht B, Stortelers C, Neyts J, Callewaert N, Saelens X. Sci Transl Med. 2021 Nov 24;13(621):eabi7826
- A nanobody toolbox targeting dimeric coiled-coil modules for functionalization of designed protein origami structures. Majerle A, Hadži S, Aupič J, Satler T, Lapenta F, Strmšek Ž, Lah J, Loris R, Jerala R. Proc Natl Acad Sci U S A. 2021 Apr 27;118(17):e2021899118.
- A vulnerable, membrane-proximal site in human respiratory syncytial virus F revealed by a prefusion-specific single-domain antibody. Rossey I, Hsieh CL, Sedeyn K, Ballegeer M, Schepens B, Mclellan JS, Saelens X. J Virol. 2021 Mar 10;95(11):e02279-20
- Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies. Wrapp D, De Vlieger D, Corbett KS, Torres GM, Wang N, Van Breedam W, Roose K, van Schie L; VIB-CMB COVID-19 Response Team, Hoffmann M, Pöhlmann S, Graham BS, Callewaert N, Schepens B, Saelens X, McLellan JS. Cell. 2020 May 28;181(5):1004-1015.e15
- Nanobody-Mediated Neutralization Reveals an Achilles Heel for Norovirus. Koromyslova AD, Devant JM, Kilic T, Sabin CD, Malak V, Hansman GS. J Virol. 2020 Jun 16;94(13):e00660-20.
- Development of anti-matrix metalloproteinase-2 (MMP-2) VHHs as potential therapeutic and diagnostic tools. Marturano A, Hendrickx M, Falcinelli E, Sebastiano M, Guglielmini G, Hassanzadeh Ghassabeh G, Muyldermans S, Declerck P, Gresele P. NANOMEDICINE-UK, 102103, 24,2020
- Targeting Neuropilin-1 with VHHs Reduces Colorectal Carcinoma Development. De V*, Bonelli S*, Awad R, Dewilde M, Rizzolio S, Lecocq Q, Bolli E, Santos A, Laoui D, Schoonooghe S, Tamagnone L, Goyvaerts C, Mazzone M, BRECKPOT K, Van Ginderachter J. Cancers, 3582, 12, 2020
- Identification of VHHs against the Acute Myeloid Leukemia Marker CD33. Romão E*, Krasniqi A*, Maes L, Vandenbrande C, Sterckx Y, Stijlemans B, Vincke C, Devoogdt N, Muyldermans S. INT J MOL SCI, 21, 2020
- Single-domain antibody fusion proteins can target and shuttle functional proteins into macrophage mannose receptor expressing macrophages. De V, Lecocq Q, Giron P, Heirman C, Geeraerts X, Bolli E, Movahedi K, Massa S, Schoonooghe S, Thielemans K, Goyvaerts C, Van Ginderachter J, Breckpot K. J CONTROL RELEASE, 107-120, 299, 2019
- An innovative approach in the detection of Toxocara canis excretory/secretory antigens using specific VHHs. Morales-yanez F, Sariego I, Vincke C, Hassanzadeh Ghassabeh G, Polman K, Muyldermans S. INT J PARASITOL, 635-645, 49, 2019