title: Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells.
abstract: Lentiviral vectors (LVs) provide unique opportunities for the development of immunotherapeutic strategies, as they transduce a variety of cells in situ, including antigen-presenting cells (APCs). Engineering LVs to specifically transduce APCs is required to promote their translation towards the clinic. We report on the Nanobody (Nb) display technology to target LVs to dendritic cells (DCs) and macrophages. This innovative approach exploits the budding mechanism of LVs to incorporate an APC-specific Nb and a binding-defective, fusion-competent form of VSV.G in the viral envelope. In addition to production of high titer LVs, we demonstrated selective, Nb-dependent transduction of mouse DCs and macrophages both in vitro and in situ. Moreover, this strategy was translated to a human model in which selective transduction of in vitro generated or lymph node (LN)-derived DCs and macrophages, was demonstrated. In conclusion, the Nb display technology is an attractive approach to generate LVs targeted to specific cell types.
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Goyvaerts
authors.forename: K
authors.initials: K
authors.lastname: De Groeve
authors.forename: J
authors.initials: J
authors.lastname: Dingemans
authors.forename: S
authors.initials: S
authors.lastname: Van Lint
authors.forename: L
authors.initials: L
authors.lastname: Robays
authors.forename: C
authors.initials: C
authors.lastname: Heirman
authors.forename: J
authors.initials: J
authors.lastname: Reiser
authors.forename: X-Y
authors.initials: XY
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Thielemans
authors.forename: P
authors.initials: P
authors.lastname: De Baetselier
authors.forename: G
authors.initials: G
authors.lastname: Raes
authors.forename: K
authors.initials: K
authors.lastname: Breckpot
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008264:Macrophages; D051379:Mice; D061905:Single-Domain Antibodies; D014161:Transduction, Genetic
chemical_list: D061905:Single-Domain Antibodies