Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen

Sandeep S Saluja,1 Douglas J Hanlon,1 Fiona A Sharp,2 Enping Hong,2 David Khalil,1 Eve Robinson,1 Robert Tigelaar,1 Tarek M Fahmy,2,3 Richard L Edelson1 1Department of Dermatology, Yale University School of Medicine, 2Department of Biomedical Engineering, Yale University, 3Department of I...

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Autores principales:	Saluja SS, Hanlon DJ, Sharp FA, Hong E, Khalil D, Robinson E, Tigelaar R, Fahmy TM, Edelson RL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/28df43de85bd483294bbcc482ad39c70
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spelling	oai:doaj.org-article:28df43de85bd483294bbcc482ad39c702021-12-02T03:54:13ZTargeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen1178-2013https://doaj.org/article/28df43de85bd483294bbcc482ad39c702014-11-01T00:00:00Zhttp://www.dovepress.com/targeting-human-dendritic-cells-via-dec-205-using-plga-nanoparticles-l-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Sandeep S Saluja,1 Douglas J Hanlon,1 Fiona A Sharp,2 Enping Hong,2 David Khalil,1 Eve Robinson,1 Robert Tigelaar,1 Tarek M Fahmy,2,3 Richard L Edelson1 1Department of Dermatology, Yale University School of Medicine, 2Department of Biomedical Engineering, Yale University, 3Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA Abstract: Targeting antigen to dendritic cells (DCs) is a powerful and novel strategy for vaccination. Priming or loading DCs with antigen controls whether subsequent immunity will develop and hence whether effective vaccination can be achieved. The goal of our present work was to increase the potency of DC-based antitumor vaccines by overcoming inherent limitations associated with antigen stability and cross-presentation. Nanoparticles prepared from the biodegradable polymer poly(lactic-co-glycolic acid) have been extensively used in clinical settings for drug delivery and are currently the subject of intensive investigation as antigen delivery vehicles for vaccine applications. Here we describe a nanoparticulate delivery system with the ability to simultaneously carry a high density of protein-based antigen while displaying a DC targeting ligand on its surface. Utilizing a targeting motif specific for the DC-associated surface ligand DEC-205, we show that targeted nanoparticles encapsulating a MART-127–35 peptide are both internalized and cross-presented with significantly higher efficiency than isotype control-coated nanoparticles in human cells. In addition, the DEC-205-labeled nanoparticles rapidly escape from the DC endosomal compartment and do not colocalize with markers of early (EEA-1) or late endosome/lysosome (LAMP-1). This indicates that encapsulated antigens delivered by nanoparticles may have direct access to the class I cytoplasmic major histocompatibility complex loading machinery, overcoming the need for “classical” cross-presentation and facilitating heightened DC stimulation of anti-tumor CD8+ T-cells. These results indicate that this delivery system provides a flexible and versatile methodology to deliver melanoma-associated antigen to DCs, with both high efficiency and heightened potency. Keywords: dendritic cells, DEC-205, PLGA nanoparticles, cross-presentation, melanoma-associated antigenSaluja SSHanlon DJSharp FAHong EKhalil DRobinson ETigelaar RFahmy TMEdelson RLDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 5231-5246 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Saluja SS Hanlon DJ Sharp FA Hong E Khalil D Robinson E Tigelaar R Fahmy TM Edelson RL Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen
description	Sandeep S Saluja,1 Douglas J Hanlon,1 Fiona A Sharp,2 Enping Hong,2 David Khalil,1 Eve Robinson,1 Robert Tigelaar,1 Tarek M Fahmy,2,3 Richard L Edelson1 1Department of Dermatology, Yale University School of Medicine, 2Department of Biomedical Engineering, Yale University, 3Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA Abstract: Targeting antigen to dendritic cells (DCs) is a powerful and novel strategy for vaccination. Priming or loading DCs with antigen controls whether subsequent immunity will develop and hence whether effective vaccination can be achieved. The goal of our present work was to increase the potency of DC-based antitumor vaccines by overcoming inherent limitations associated with antigen stability and cross-presentation. Nanoparticles prepared from the biodegradable polymer poly(lactic-co-glycolic acid) have been extensively used in clinical settings for drug delivery and are currently the subject of intensive investigation as antigen delivery vehicles for vaccine applications. Here we describe a nanoparticulate delivery system with the ability to simultaneously carry a high density of protein-based antigen while displaying a DC targeting ligand on its surface. Utilizing a targeting motif specific for the DC-associated surface ligand DEC-205, we show that targeted nanoparticles encapsulating a MART-127–35 peptide are both internalized and cross-presented with significantly higher efficiency than isotype control-coated nanoparticles in human cells. In addition, the DEC-205-labeled nanoparticles rapidly escape from the DC endosomal compartment and do not colocalize with markers of early (EEA-1) or late endosome/lysosome (LAMP-1). This indicates that encapsulated antigens delivered by nanoparticles may have direct access to the class I cytoplasmic major histocompatibility complex loading machinery, overcoming the need for “classical” cross-presentation and facilitating heightened DC stimulation of anti-tumor CD8+ T-cells. These results indicate that this delivery system provides a flexible and versatile methodology to deliver melanoma-associated antigen to DCs, with both high efficiency and heightened potency. Keywords: dendritic cells, DEC-205, PLGA nanoparticles, cross-presentation, melanoma-associated antigen
format	article
author	Saluja SS Hanlon DJ Sharp FA Hong E Khalil D Robinson E Tigelaar R Fahmy TM Edelson RL
author_facet	Saluja SS Hanlon DJ Sharp FA Hong E Khalil D Robinson E Tigelaar R Fahmy TM Edelson RL
author_sort	Saluja SS
title	Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen
title_short	Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen
title_full	Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen
title_fullStr	Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen
title_full_unstemmed	Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen
title_sort	targeting human dendritic cells via dec-205 using plga nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/28df43de85bd483294bbcc482ad39c70
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Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen

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