Glycan-modified liposomes boost CD4+ and CD8+ T-cell responses by targeting DC-SIGN on dendritic cells

Unger, Wendy W. J.; Beelen, Astrid J. van; Bruijns, Sven C. M.; Joshi, Medha; Fehres, Cynthia M.; Bloois, Louis van; Verstege, Marleen I.; Ambrosini, Martino; Kalay, Hakan; Nazmi, Kamran; Bolscher, Jan G. M.; Hooijberg, Erik; Gruijl, Tanja D. de; Storm, Gert; Kooyk, Yvette van

doi:10.1016/j.jconrel.2012.02.007

Cited by 151 publications

(126 citation statements)

References 41 publications

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“…[25][26][27][28][29] In addition, we showed that in combination with an adjuvant, DC-SIGN triggering modulates cytokine responses 26 and elicits strong CD4 C and CD8 C effector T cell responses in murine and human models. 23,26 However, whether targeting antigens to CLRs such as DC-SIGN using glycans yields superior tumor immunity than using specific antibodies is not known at present.…”

Section: Introductionmentioning

confidence: 87%

“…Presence of antibody or glycan on OVA was determined by ELISA, as described. 28,26 Antigen-presentation assays T-cell proliferation assays were performed as previously described. 28 In short, DC were pulsed with indicated Vaccination and tumor therapy Mice were injected s.c. either with 100 mg OVA-LeB or 10 mg OVA-aDC-SIGN mixed with 25 mg anti-CD40 Ab (1C10) on day 0 and day 14.…”

Section: Generation Of Neo-glycoconjugatesmentioning

confidence: 99%

“…C T cells, lymphocytes were re-stimulated with 1.0 mg/mL OVA 257-264, TRP-2 180-188 , gp100 [25][26][27][28][29][30][31][32] , respectively in the presence of 5 mg/ml Brefeldin A (BD PharMingen) for 4-5 h. To address the presence of polyclonal IFNg producing CD8…”

Section: T Cell Restimulationmentioning

confidence: 99%

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Antigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression

et al. 2014

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C regulatory T cells (Tregs), resulting in defective T cell priming and failure to induce tumor regression. To circumvent these problems we evaluated a novel combinatorial therapeutic strategy. We show that tumor antigen targeting to DC-SIGN in humanized hSIGN mice via glycans or specific antibodies induces superior T cell priming. Next, this targeted therapy was combined with transient Foxp3 C Treg depletion employing hSIGNxDEREG mice. While Treg depletion alone slightly delayed B16-OVA melanoma growth, only the combination therapy instigated long-term tumor regression in a substantial fraction of mice. This novel strategy resulted in optimal generation of antigen-specific activated CD8C T cells which accumulated in regressing tumors. Notably, Treg depletion also allowed the local appearance of effector T cells specific for endogenous B16 antigens. This indicates that antitumor immune responses can be broadened by therapies aimed at controlling Tregs in tumor environments. Thus, transient inhibition of Treg-mediated immune suppression potentiates DC targeted antigen vaccination and tumor-specific immunity.

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Section: Introductionmentioning

confidence: 87%

Section: Generation Of Neo-glycoconjugatesmentioning

confidence: 99%

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Antigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression

et al. 2014

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“…Cell surface TLRs and the C-type lectin receptors (CLRs) are of major interest for targeting [1,12]. Surface decoration of delivery vehicles with antibody fragments specific for particular CLR is showing high potential; glycan-modified particle surfaces are also being studied, particularly for targeting DC-SIGN [13]. The prime aim of such targeting is to enhance endocytosis of the delivered material by DC.…”

Section: Nanoparticle-based Deliverymentioning

confidence: 99%

Functional RNA Delivery Targeted to Dendritic Cells By Synthetic Nanoparticles

McCullough¹,

Bassi²,

Démoulins³

et al. 2012

Therapeutic Delivery

102

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ReviewTargeting the immune system Dendritic cells (DCs) play crucial roles in promoting and regulating immune defenses, providing important targets for prophylactic and therapeutic approaches (FiguRe 1). Particulate formulations, including liposomes and other nanoparticles, have been employed as delivery vehicles. Despite the large number of reports, current in-depth knowledge on the cellular processes involved remains relatively limited, particularly for nucleic acid delivery. Certain structures in the nucleic acid may also signal the cell in the sense of an adjuvant or immunomodulatory activity. Importantly, the optimized characteristics for delivery of an antigen or therapeutic agent may be distinct from those for nucleic acid delivery, especially RNA species. Moreover, RNA delivery for interference therapy will not necessarily require the same delivery routes as mRNA delivery wherein RNA translation is the main requisite.The efficacy of delivery can be further improved by targeting the appropriate cells of the immune system, an area in which nanoparticle-based delivery platforms have found an important niche [1]. Advances with prophylactic applications can also prove valuable for therapeutic applications and vice versa, as seen with RNA delivery. This review will consider how growing knowledge on delivery mechanisms has found application with nucleic acids, in both prophylaxis and therapy, focusing on interaction with DCs.The initial components of the DC endocytic pathways are critically important in determining how the cell handles the delivered material; thereafter, correct cytosolic delivery is a critical element for a number of desired outcomes, including delivery of nucleic acids. Advances made with protein delivery -in particular, vaccines -are of value to highlight the potential of a particular mode of application or the high risk for nucleic acid integrity. Particularly pertinent is the application of cationic elements in the delivery mechanisms and how application of ligands for cell receptors influence intracellular compartmentalization.It is not the aim of the present review to retrace all the fine details of work contributing to our current knowledge. Accordingly, review articles covering areas that have already received considerable attention will be employed and assimilated to provide a more elaborate picture of the current situation. This will allow a focusing on more recent advances, along with problems and pitfalls therein. While advances on protein and DNA delivery will be presented, these will be used to highlight how our current knowledge can be applied to RNA delivery. There are numerous reviews on protein delivery to DC, wherein many of the procedures employed are not relevant for RNA delivery, which must escape into the cytosol undamaged. With DNA delivery, there is also the question of whether the DNA will activate the DC or reach the nucleus for transcription; this latter area has most often Functional RNA delivery targeted to dendritic cells by synthetic nanoparticles Dendritic cell...

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“…Due to the precise design of the surface of nanoparticles, DC targeting can be achieved via conjugation with the ligands of the mannose receptor, Fc receptor (FcR), CD11c/CD18 receptor, and DC-SIGN onto the nanoparticle surface. [29][30][31][32][33][34][35][36][37] To further facilitate antigen entry into a cell, cell-penetrating peptides (CPPs) and viral-like nanosurfaces have been applied. 23,24,[38][39][40] More recently, smart nanoparticles have been manufactured using pH-sensitive or redox-sensitive materials; 23,24,[40][41][42][43] these environment-responsive nanoparticles enable controlled release of antigens at target sites and more adequate release of antigens from endo-lysosomal compartments, thus enhancing antigen presentation.…”

Section: Introductionmentioning

confidence: 99%

Applications of nanomaterials as vaccine adjuvants

Zhu

Wang

Nie³

2014

Human Vaccines & Immunotherapeutics

132

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Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigenspecific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials' physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants.

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Glycan-modified liposomes boost CD4+ and CD8+ T-cell responses by targeting DC-SIGN on dendritic cells

Cited by 151 publications

References 41 publications

Antigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression

Antigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression

Functional RNA Delivery Targeted to Dendritic Cells By Synthetic Nanoparticles

Applications of nanomaterials as vaccine adjuvants

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