Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells

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 clin...

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Main Authors: Goyvaerts, C, De Groeve, K, Dingemans, J, Van Lint, S, Robays, L, Heirman, C, Reiser, J, Zhang, X-Y, Thielemans, K, De Baetselier, P, Raes, G, Breckpot, K
Format: Online
Language:English
Published: Nature Publishing Group 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520013/
id pubmed-3520013
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spelling pubmed-35200132012-12-12 Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells Goyvaerts, C De Groeve, K Dingemans, J Van Lint, S Robays, L Heirman, C Reiser, J Zhang, X-Y Thielemans, K De Baetselier, P Raes, G Breckpot, K Original Article 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. Nature Publishing Group 2012-12 2012-01-12 /pmc/articles/PMC3520013/ /pubmed/22241177 http://dx.doi.org/10.1038/gt.2011.206 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Goyvaerts, C
De Groeve, K
Dingemans, J
Van Lint, S
Robays, L
Heirman, C
Reiser, J
Zhang, X-Y
Thielemans, K
De Baetselier, P
Raes, G
Breckpot, K
spellingShingle Goyvaerts, C
De Groeve, K
Dingemans, J
Van Lint, S
Robays, L
Heirman, C
Reiser, J
Zhang, X-Y
Thielemans, K
De Baetselier, P
Raes, G
Breckpot, K
Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells
author_facet Goyvaerts, C
De Groeve, K
Dingemans, J
Van Lint, S
Robays, L
Heirman, C
Reiser, J
Zhang, X-Y
Thielemans, K
De Baetselier, P
Raes, G
Breckpot, K
author_sort Goyvaerts, C
title Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells
title_short Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells
title_full Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells
title_fullStr Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells
title_full_unstemmed Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells
title_sort development of the nanobody display technology to target lentiviral vectors to antigen-presenting cells
description 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.
publisher Nature Publishing Group
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520013/
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