Nanoporous polyelectrolyte vaccine microcarriers. A formulation platform for enhancing humoral and cellular immune responses

Koker, Stefaan De; Fierens, Kaat; Dierendonck, Marijke; Rycke, Riet De; Lambrecht, Bart N.; Grooten, Johan; Remon, Jean Paul; Geest, Bruno G. De

doi:10.1016/j.jconrel.2014.07.043

Cited by 15 publications

(10 citation statements)

References 32 publications

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“…In a first series of experiments we examined whether spray drying of living cancer cells was feasible applying similar conditions as previously determined in our laboratories for spray‐drying of soluble proteins and polymers . An LLC.OVA cell suspension, at a density of 60 × 10 6 cells per 10 mL deionized water, was stirred on ice to minimize cell lysis and aggregation.…”

Section: Resultsmentioning

confidence: 99%

“…Whereas soluble antigens are predominantly presented via MHC‐II peptide complexes by DCs to CD4+ T‐cells, formulation of soluble antigens into microparticles is known to enhance cross‐presentation via MHC‐I by DCs. The latter is essential for the priming of cytotoxic CD8+ T‐cells that hold the capacity to recognize tumor cells and eliminate these via secretion of perforin and granzymes . Here we investigated whether encapsulation of cell lysate into polyelectrolyte microparticles also promoted antigen presentation via MHC‐I.…”

Section: Resultsmentioning

confidence: 99%

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Polyelectrolyte‐Enrobed Cancer Cells in View of Personalized Immune‐Therapy

et al. 2017

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Targeting the immune system with a personalized vaccine containing cues derived from the patient's malignancy might be a promising approach in the fight against cancer. It includes neo‐antigens as well as nonmutated tumor antigens, preferentially leading to an immune response that is directed to a broader range of epitopes compared to strategies involving a single antigen. Here, this paper reports on an elegant method to encapsulate whole cancer cells into polyelectrolyte particles. Porous and nonaggregated microparticles containing dead cancer cells are obtained by admixing mannitol and live cancer cells with oppositely charged polyelectrolytes, dextran sulfate (anionic polysaccharide), and poly‐l‐arginine (cationic polypeptide) prior to atomization into a hot air stream. It shows that the polyelectrolyte‐enrobed cancer cells, upon redispersion in phosphate buffered saline buffer, are stable and do not release cell proteins in the supernatant. In vitro experiments reveal that the particles are nontoxic and strongly increase uptake of cell lysate by dendritic cells. In vitro assessment of antigen presentation by dendritic cells reveal the potential of the polyelectrolyte‐enrobed cancer cells as promotors of antigen cross‐presentation. Finally, it is demonstrated that the immunogenicity can be enhanced by surface adsorption of a polymer‐substituted TLR7‐agonist.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Polyelectrolyte‐Enrobed Cancer Cells in View of Personalized Immune‐Therapy

et al. 2017

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“…Further reasons for increased but seemingly futile cellmediated immune responses to reZP in comparison to pZP are speculative. Differences in the particulate nature of these vaccines, such as solubility or levels of aggregation, may influence antigen uptake by APC's and subsequent CD4 + and CD8 + T-cell stimulation [29]. Similarly, differences in the quaternary structures of recombinant versus native ZP proteins, influenced by their respective levels and patterns of glycosylation, may affect both B-and T-cell immune responses.…”

Section: Discussionmentioning

confidence: 99%

Antigen-specific CD4+ and CD8+ T-cell responses in PBMC from pony mares immunized with either native or recombinant zona pellucida vaccines

et al. 2019

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Highlights • Cell-mediated immune response to zona pellucida-based vaccines was investigated using CFSE dilution and immunophenotyping. • Significant anamnestic antigen-specific CD4 + and CD8 + T-lymphocyte responses were detected. • Data suggest that CTL may play a role in ovarian suppression observed during pZP immunocontraception in the mare. • Further investigation into the role of CTL during zona pellucida-based immunocontraception is warranted.

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“…Indeed, this concept has already been applied on the macroscale for the development of efficacious and pain-free LbL-microneedle mediated vaccination [138,139]. Interest for colloidal LbL vaccines has previously focused on the stabilization and coating of antigen-salt precipitates [140–142] or polyelectrolyte–antigen complexes [143], but recent work [144,145] describing the direct incorporation of antigen peptides into LbL films on nano- and submicrometer templates is yielding interesting results. For example, an LbL nanoparticle vaccine was recently described by Zhang et al [146], where the LbL film was constructed entirely from immunologically active polymers in order to simultaneously deliver both adjuvant and antigen.…”

Section: The Lbl Film As a Vector For Drugs And Combination Therapymentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Engineering nanolayered particles for modular drug delivery

Correa

Dreaden

et al. 2016

Journal of Controlled Release

111

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Layer-by-layer (LbL) based self-assembly of nanoparticles is an emerging and powerful method to develop multifunctional and tissue responsive nanomedicines for a broad range of diseases. This unique assembly technique is able to confer a high degree of modularity, versatility, and compositional heterogeneity to nanoparticles via the sequential deposition of alternately charged polyelectrolytes onto a colloidal template. LbL assembly can provide added functionality by directly incorporating a range of functional materials within the multilayers including nucleic acids, synthetic polymers, polypeptides, polysaccharides, and functional proteins. These materials can be used to generate hierarchically complex, heterogeneous thin films on an extensive range of both traditional and novel nanoscale colloidal templates, providing the opportunity to engineer highly precise systems capable of performing the numerous tasks required for systemic drug delivery. In this review, we will discuss the recent advancements towards the development of LbL nanoparticles for drug delivery and diagnostic applications, with a special emphasis on the incorporation of biostability, active targeting, desirable drug release kinetics, and combination therapies into LbL nanomaterials. In addition to these topics, we will touch upon the next steps for the translation of these systems towards the clinic.

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Nanoporous polyelectrolyte vaccine microcarriers. A formulation platform for enhancing humoral and cellular immune responses

Cited by 15 publications

References 32 publications

Polyelectrolyte‐Enrobed Cancer Cells in View of Personalized Immune‐Therapy

Polyelectrolyte‐Enrobed Cancer Cells in View of Personalized Immune‐Therapy

Antigen-specific CD4+ and CD8+ T-cell responses in PBMC from pony mares immunized with either native or recombinant zona pellucida vaccines

Engineering nanolayered particles for modular drug delivery

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