scholarly journals Achieving dendritic cell subset-specific targeting in vivo by site-directed conjugation of targeting antibodies to nanocarriers

Nano Today ◽  
2022 ◽  
Vol 43 ◽  
pp. 101375
Author(s):  
Johanna Simon ◽  
Michael Fichter ◽  
Gabor Kuhn ◽  
Maximilian Brückner ◽  
Cinja Kappel ◽  
...  
2021 ◽  
Author(s):  
Johanna Simon ◽  
Michael Fichter ◽  
Gabor Kuhn ◽  
Maxmimilian Brueckner ◽  
Cinja Kappel ◽  
...  

The major challenge of nanocarrier-based anti-cancer vaccination approaches is the targeted delivery of antigens and immunostimulatory agents to cells of interest, such as specific subtypes of dendritic cells (DCs), in order to induce robust antigen-specific anti-tumor responses. An undirected cell and body distribution of nanocarriers can lead to unwanted delivery to other immune cell types like macrophages reducing the vaccine efficacy. An often-used approach to overcome this issue is the surface functionalization of nanocarriers with targeting moieties, such as antibodies, mediating cell type-specific interaction. Numerous studies could successfully prove the targeting efficiency of antibody-conjugated carrier systems in vitro, however, most of them failed when targeting DCs in vivo that is partly due to cells of the reticuloendothelial system unspecifically clearing nanocarriers from the blood stream via Fc receptor ligation. Therefore, this study shows a surface functionalization strategy to site-specifically attach antibodies in an orientated direction onto the nanocarrier surface. Different DC-targeting antibodies, such as anti-CD11c, anti-CLEC9A, anti-DEC205 and anti-XCR1, were conjugated to the nanocarrier surface at their Fc domains. Anti-mouse CD11c antibody-conjugated nanocarriers specifically accumulated in the targeted organ (spleen) over time. Additionally, antibodies against CD11c and CLEC9A proved to specifically direct nanocarriers to the targeted DC subtype, conventional DCs type 1. In conclusion, site-directed antibody conjugation to nanocarriers is essential in order to avoid unspecific uptake by non-target cells while achieving antibody-specific targeting of DC subsets. This novel conjugation technique paves the way for the development of antibody-functionalized nanocarriers for DC-based vaccination approaches in the field of cancer immunotherapy.


2009 ◽  
Vol 21 (2) ◽  
pp. 167-177 ◽  
Author(s):  
F. Guimont-Desrochers ◽  
C. Beauchamp ◽  
G. Chabot-Roy ◽  
V. Dugas ◽  
E. E. Hillhouse ◽  
...  

2002 ◽  
Vol 195 (4) ◽  
pp. 507-516 ◽  
Author(s):  
Winfried Barchet ◽  
Marina Cella ◽  
Bernhard Odermatt ◽  
Carine Asselin-Paturel ◽  
Marco Colonna ◽  
...  

An effective type I interferon (IFN-α/β) response is critical for the control of many viral infections. Here we show that in vesicular stomatitis virus (VSV)-infected mouse embryonic fibroblasts (MEFs) the production of IFN-α is dependent on type I IFN receptor (IFNAR) triggering, whereas in infected mice early IFN-α production is IFNAR independent. In VSV-infected mice type I IFN is produced by few cells located in the marginal zone of the spleen. Unlike other dendritic cell (DC) subsets, FACS®-sorted CD11cintCD11b−GR-1+ DCs show high IFN-α expression, irrespective of whether they were isolated from VSV-infected IFNAR-competent or -deficient mice. Thus, VSV preferentially activates a specialized DC subset presumably located in the marginal zone to produce high-level IFN-α largely independent of IFNAR feedback signaling.


2004 ◽  
Vol 77 (4) ◽  
pp. 535-543 ◽  
Author(s):  
Mauritius Menges ◽  
Thomas Baumeister ◽  
Susanne Rössner ◽  
Patrizia Stoitzner ◽  
Nikolaus Romani ◽  
...  

2021 ◽  
Author(s):  
Müge Özkan ◽  
Yusuf Cem Eskiocak ◽  
Gerhard Wingender

Asthma is a heterogeneous disease with neutrophilic and eosinophilic asthma as the main endotypes that are distinguished according to the cells recruited to the airways and the related pathology. Eosinophilic asthma is the treatment-responsive endotype, which is mainly associated with allergic asthma. Neutrophilic asthma is a treatment-resistant endotype, affecting 5-10% of asthmatics. Although eosinophilic asthma is well-studied, a clear understanding of the endotypes is essential to devise effective diagnosis and treatment approaches for neutrophilic asthma. To this end, we directly compared adjuvant-induced mouse models of neutrophilic (CFA/OVA) and eosinophilic (Alum/OVA) asthma side-by-side. The immune response in the inflamed lung was analyzed by multi-parametric flow cytometry and immunofluorescence. We found that eosinophilic asthma was characterized by a preferential recruitment of interstitial macrophages and myeloid dendritic cells, whereas in neutrophilic asthma plasmacytoid dendritic cells, exudate macrophages, and GL7 + activated B cells predominated. This differential distribution of macrophage and dendritic cell subsets reveals important aspects of the pathophysiology of asthma and holds the promise to be used as biomarkers to diagnose asthma endotypes.


2016 ◽  
Vol 94 (5) ◽  
pp. 447-457 ◽  
Author(s):  
Christian Bryant ◽  
Phillip D Fromm ◽  
Fiona Kupresanin ◽  
Georgina Clark ◽  
Kenneth Lee ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document