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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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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520013/
https://www.ncbi.nlm.nih.gov/pubmed/22241177
http://dx.doi.org/10.1038/gt.2011.206
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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
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
collection PubMed
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.
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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 Gene Ther 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/
spellingShingle Original Article
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
title 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_short 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
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520013/
https://www.ncbi.nlm.nih.gov/pubmed/22241177
http://dx.doi.org/10.1038/gt.2011.206
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