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Abstract
Dendritic cells (DC) play key roles in various aspects of immunity. At present, ex vivo-generated, antigen-loaded DCs have been used as vaccines to improve immunity and studies in mice have shown that DCs loaded with tumour antigens can induce protective anti-tumour immunity. Nevertheless, to date, clinical responses have only been observed in a minority of patients. The in situ delivery of antigens towards in vivo DCs is a promising alternative for immunotherapy. Furthermore, antigen-specific immunotherapy with antibodies allows specific targeting of DCs depending on their cell surface marker expression. However, this strategy requires a good understanding of the various DC subsets, their localization and the different surface markers they express and molecular probes to specifically target them. Nanobodies are single-domain antigen-binding fragments derived from naturally occurring heavy chain antibodies in Camelidae, constituting exquisite targeting moieties for therapeutic and diagnostic applications (Reviewed in the second part of chapter 1). In this thesis, we aimed to evaluate the application of Nanobodies as molecular probes to target dendritic cells.
Our first aim was to generate Nanobodies recognising specifically dendritic cell populations in vivo and to evaluate their potential as carrier for targeted delivery of antigens to dendritic cells. In the first experimental part, anti-DC Nanobodies were isolated from phage display libraries by cell panning on DCs and we investigated their binding profile on a range of in vitro and ex vivo cell populations. Selected anti-DC Nanobodies were then genetically fused with a model antigen to evaluate their potential of antigen delivery to DCs in vitro.
Our second aim was to explore the potential of Nanobodies as molecular probes to visualize DC populations in vivo. By single photon emission computed tomography we evaluated the biodistribution of radionuclide labelled Nanobodies in naïve animals. In order to ascertain the observed biodistribution was due to specific recognition of the target, the antigen-binding loops of the anti-DC Nanobodies were grafted on a model Nanobody scaffold and their biodistribution was re-evaluated.
Finally, to target and characterize different DC populations, a novel library of a specific subset of Nanobodies against a subpopulation of DCs was generated. This led to retrieval of Nanobodies of a different class which are DC-specific.
Original language | English |
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Place of Publication | Brussels |
Publication status | Published - 2010 |
Keywords
- anti-DC nanobodies
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Dive into the research topics of 'Nanobodies as molecular probes for targeting of dendritic cells'. Together they form a unique fingerprint.Activities
- 1 Member of PhD committee
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Nanobodies as molecular probes for targeting of dendritic cells (Event)
Luc Leyns (Jury), Kurt De Groeve (Presenter), Patrick De Baetselier (Supervisor) & Geert Raes (Supervisor)
8 Jul 2010Activity: Membership › Member of PhD committee