Nanoparticle-Mediated Combinatorial Targeting of Multiple Human Dendritic Cell (DC) Subsets Leads to Enhanced T Cell Activation via IL-15–Dependent DC Crosstalk
作者： Kartik Sehgal , Ragy Ragheb , Tarek M. Fahmy , Madhav V. Dhodapkar , Kavita M. Dhodapkar
关键词:
摘要: Most vaccines depend on coadministration of Ags and adjuvants that activate APCs. Nanoparticles (NPs) have emerged as an attractive vehicle for synchronized delivery to APCs can be targeted specific cell types, such dendritic cells (DCs), which are potent Which subset human DCs should optimal activation T immunity, however, remains unknown. In this article, we describe a poly-lactic-coglycolic acid-based NP platform, wherein avidin-decorated NPs multiple DC subsets via biotinylated Abs. Both BDCA3(+) monocyte-derived DC-SIGN(+) NP-loaded were equally effective at generating Ag-specific in culture, including against complex peptide mixtures from viral tumor across MHC molecules. Ab-mediated targeting distinct led enhanced immunity. However, combination both DC-SIGN significantly greater compared with either alone. Enhanced following depended DC-mediated cytokine release was IL-15 dependent. These data demonstrate simultaneous may improve by engaging crosstalk provides novel approach improving pathogens tumors.
highwire.org参考文章(46)
Tomasz Sosinowski, Jason T. White, Eric W. Cross, Catherine Haluszczak, Philippa Marrack, Laurent Gapin, Ross M. Kedl, CD8α+ Dendritic Cell Trans Presentation of IL-15 to Naive CD8+ T Cells Produces Antigen-Inexperienced T Cells in the Periphery with Memory Phenotype and Function Journal of Immunology. ,vol. 190, pp. 1936- 1947 ,(2013) , 10.4049/JIMMUNOL.1203149
I. Jolanda M de Vries, Karen Couderé, Phillip D. Fromm, Viggo F. Van Tendeloo, Evelien L. Smits, Zwi N. Berneman, Sébastien Anguille, Eva Lion, Jurjen Tel, Interleukin-15-induced CD56(+) myeloid dendritic cells combine potent tumor antigen presentation with direct tumoricidal potential PLOS ONE. ,vol. 7, ,(2012) , 10.1371/JOURNAL.PONE.0051851
Jason Park, Thomas Mattessich, Steven M. Jay, Atu Agawu, W. Mark Saltzman, Tarek M. Fahmy, Enhancement of surface ligand display on PLGA nanoparticles with amphiphilic ligand conjugates Journal of Controlled Release. ,vol. 156, pp. 109- 115 ,(2011) , 10.1016/J.JCONREL.2011.06.025
Su M. Metcalfe, Tarek M. Fahmy, Targeted nanotherapy for induction of therapeutic immune responses Trends in Molecular Medicine. ,vol. 18, pp. 72- 80 ,(2012) , 10.1016/J.MOLMED.2011.11.002
Madhav V. Dhodapkar, Kavita M. Dhodapkar, Vaccines Targeting Cancer Stem Cells The Cancer Journal. ,vol. 17, pp. 397- 402 ,(2011) , 10.1097/PPO.0B013E318233E730
Henning Lauterbach, Barbara Bathke, Stefanie Gilles, Claudia Traidl-Hoffmann, Christian A Luber, György Fejer, Marina A Freudenberg, Gayle M Davey, David Vremec, Axel Kallies, Li Wu, Ken Shortman, Paul Chaplin, Mark Suter, Meredith O’Keeffe, Hubertus Hochrein, None, Mouse CD8α+ DCs and human BDCA3+ DCs are major producers of IFN-λ in response to poly IC Journal of Experimental Medicine. ,vol. 207, pp. 2703- 2717 ,(2010) , 10.1084/JEM.20092720
Peter Dubsky, Hiroaki Saito, Marylene Leogier, Carole Dantin, John E. Connolly, Jacques Banchereau, A. Karolina Palucka, IL-15-induced human DC efficiently prime melanoma-specific naive CD8+ T cells to differentiate into CTL. European Journal of Immunology. ,vol. 37, pp. 1678- 1690 ,(2007) , 10.1002/EJI.200636329
Karolina Palucka, Jacques Banchereau, Human dendritic cell subsets in vaccination. Current Opinion in Immunology. ,vol. 25, pp. 396- 402 ,(2013) , 10.1016/J.COI.2013.05.001
Bali Pulendran, Jason Z. Oh, Helder I. Nakaya, Rajesh Ravindran, Dmitri A. Kazmin, Immunity to viruses: learning from successful human vaccines Immunological Reviews. ,vol. 255, pp. 243- 255 ,(2013) , 10.1111/IMR.12099
Tarek M. Fahmy, Robert M. Samstein, Casey C. Harness, W. Mark Saltzman, Surface modification of biodegradable polyesters with fatty acid conjugates for improved drug targeting Biomaterials. ,vol. 26, pp. 5727- 5736 ,(2005) , 10.1016/J.BIOMATERIALS.2005.02.025