Targeting dendritic cells—why bother?

Kreutz, Martin; Tacken, Paul J.; Figdor, Carl G.

doi:10.1182/blood-2012-09-452078

Cited by 116 publications

(103 citation statements)

References 46 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, a single intradermal immunization with XCL1-OVA vaccibodies protected mice against melanoma tumor growth in both prophylactic and therapeutic settings and in the absence of intentionally added adjuvant. Whether Ag targeting to DC results in tolerance or immunity depends on parameters such as the immunogenicity of the targeting Ab (16) and the coadministration of adjuvants (37,38). Adjuvants are intended to trigger the pattern-recognition receptors that are expressed by the targeted DCs and that are normally used to detect invading microorganisms or endogenous "danger" signals.…”

Section: Discussionmentioning

confidence: 99%

Laser-Assisted Intradermal Delivery of Adjuvant-Free Vaccines Targeting XCR1+ Dendritic Cells Induces Potent Antitumoral Responses

Terhorst‐Molawi

Fossum

Barańska

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

The development of vaccines inducing efficient CD8+ T cell responses is the focus of intense research. Dendritic cells (DCs) expressing the XCR1 chemokine receptor, also known as CD103+ or CD8α+ DCs, excel in the presentation of extracellular Ags to CD8+ T cells. Because of its high numbers of DCs, including XCR1+ DCs, the skin dermis is an attractive site for vaccine administration. By creating laser-generated micropores through the epidermis, we targeted a model protein Ag fused to XCL1, the ligand of XCR1, to dermal XCR1+ DCs and induced Ag-specific CD8+ and CD4+ T cell responses. Efficient immunization required the emigration of XCR1+ dermal DCs to draining lymph nodes and occurred irrespective of TLR signaling. Moreover, a single intradermal immunization protected mice against melanoma tumor growth in prophylactic and therapeutic settings, in the absence of exogenous adjuvant. The mild inflammatory milieu created in the dermis by skin laser microporation itself most likely favored the development of potent T cell responses in the absence of exogenous adjuvants. The existence of functionally equivalent XCR1+ dermal DCs in humans should permit the translation of laser-assisted intradermal delivery of a tumor-specific vaccine targeting XCR1+ DCs to human cancer immunotherapy. Moreover, considering that the use of adjuvants in vaccines is often associated with safety issues, the possibility of inducing protective responses against melanoma tumor growth independently of the administration of exogenous adjuvants should facilitate the development of safer vaccines.

show abstract

Section: Discussionmentioning

confidence: 99%

Laser-Assisted Intradermal Delivery of Adjuvant-Free Vaccines Targeting XCR1+ Dendritic Cells Induces Potent Antitumoral Responses

Terhorst‐Molawi

Fossum

Barańska

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…DC-SIGN is a well-studied receptor that is involved both in CD4 + and CD8 + T-cell stimulation. 43 Vaccines that target DCs show considerable advantages and are considered a promising strategy for the further advancement of immunotherapy, as described by Kasternmuller et al 43 and Kreutz et al 44 In this article, we investigate specific targeting of MDDCs by DC-SIGN AuNPs in a complex 3D lung barrier coculture model. Sehgal et al, Cruz et al, and Arosio et al 39,41,45 tested DC targeting via the DC-SIGN receptor with polymer nanoparticles in DC monocultures in vitro.…”

Section: 23mentioning

confidence: 99%

Aerosol Delivery of Functionalized Gold Nanoparticles Target and Activate Dendritic Cells in a 3D Lung Cellular Model

et al. 2016

View full text Add to dashboard Cite

Nanocarrier design combined with pulmonary drug delivery holds great promise for the treatment of respiratory tract disorders. In particular, targeting of dendritic cells that are key immune cells to enhance or suppress an immune response in the lung is a promising approach for the treatment of allergic diseases. Fluorescently encoded poly(vinyl alcohol) (PVA)-coated gold nanoparticles, functionalized with either negative (−COO − ) or positive (−NH 3 + ) surface charges, were functionalized with a DC-SIGN antibody on the particle surface, enabling binding to a dendritic cell surface receptor. A 3D coculture model consisting of epithelial and immune cells (macrophages and dendritic cells) mimicking the human lung epithelial tissue barrier was employed to assess the effects of aerosolized AuNPs. PVA-NH 2 AuNPs showed higher uptake compared to that of their −COOH counterparts, with the highest uptake recorded in macrophages, as shown by flow cytometry. None of the AuNPs induced cytotoxicity or necrosis or increased cytokine secretion, whereas only PVA-NH 2 AuNPs induced higher apoptosis levels. DC-SIGN AuNPs showed significantly increased uptake by monocyte-derived dendritic cells (MDDCs) with subsequent activation compared to non-antibody-conjugated control AuNPs, independent of surface charge. Our results show that DC-SIGN conjugation to the AuNPs enhanced MDDC targeting and activation in a complex 3D lung cell model. These findings highlight the potential of immunoengineering approaches to the targeting and activation of immune cells in the lung by nanocarriers.

show abstract

“…Consequently, strategies need to be developed that exclusively act on TiDCs, preferably on CD8a þ TiDCs, which are critical for the stimulation of antitumor immunity (8,9). Several strategies have been developed to target adjuvants like TLR ligands or IL12, together with antigens, to cross-priming DCs (10)(11)(12)(13)(14)(15). Often these exploit antibodies or nanobodies to surface markers differentially expressed by DC subsets (13,15).…”

Section: Introductionmentioning

confidence: 99%

Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells

Lint

Renmans

Broos

et al. 2016

Cancer Immunology Research

View full text Add to dashboard Cite

show abstract

Targeting dendritic cells—why bother?

Cited by 116 publications

References 46 publications

Laser-Assisted Intradermal Delivery of Adjuvant-Free Vaccines Targeting XCR1+ Dendritic Cells Induces Potent Antitumoral Responses

Laser-Assisted Intradermal Delivery of Adjuvant-Free Vaccines Targeting XCR1+ Dendritic Cells Induces Potent Antitumoral Responses

Aerosol Delivery of Functionalized Gold Nanoparticles Target and Activate Dendritic Cells in a 3D Lung Cellular Model

Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells

Contact Info

Product

Resources

About