PEGylated tumor cell membrane vesicles as a new vaccine platform for cancer immunotherapy

Ochyl, Lukasz J.; Bazzill, Joseph; Park, Charles; Xu, Yao; Kuai, Rui; Moon, James J.

doi:10.1016/j.biomaterials.2018.08.016

Cited by 85 publications

(84 citation statements)

References 34 publications

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“…M1 NVs successfully repolarized TAMs toward M1 phenotypes, which potentiated the effect of an immune checkpoint blockade. Moon and co‐workers harvested melanoma tumor cells to synthesize PEG‐coated tumor‐derived NVs with the aim of overcoming the poor immunogenicity of whole tumor cell lysate . The authors revealed that the PEG‐coated NVs not only induced more robust antigen‐specific CD8 + CTLs, but also prevented all surviving mice from a rechallenge of tumor cells when combined with immune checkpoint blockade therapy.…”

Section: Nanoscale Materials For Immunotherapymentioning

confidence: 99%

“…Moon and coworkers harvested melanoma tumor cells to synthesize PEGcoated tumor-derived NVs with the aim of overcoming the poor immunogenicity of whole tumor cell lysate. [237] The authors revealed that the PEG-coated NVs not only induced more robust antigen-specific CD8 + CTLs, but also prevented all surviving mice from a rechallenge of tumor cells when combined with immune checkpoint blockade therapy. Soon after, the www.advmat.de www.advancedsciencenews.com same group developed mature dendritic cell-derived NVs (DCderived NVs) loaded with antigenic peptides to upregulate the expression of costimulatory receptors on dendritic cells and to enhance the cross-priming of T cells in vitro.…”

Section: Cell-derived Nanovesicles With Liquid Coresmentioning

confidence: 99%

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Materials for Immunotherapy

et al. 2019

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Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation. The materials are organized based on their characteristic length scale, whereby the enabling feature of each technology is organized by the structure of that material. For example, the mechanisms by which i) nanoscale materials can improve targeting and infiltration of immunomodulatory payloads into tissues and cells, ii) microscale materials can facilitate cell‐mediated transport and serve as artificial antigen‐presenting cells, and iii) macroscale materials can form the basis of artificial microenvironments to promote cell infiltration and reprogramming are discussed. As a step toward establishing a set of design rules for future immunotherapies, materials that intrinsically activate or suppress the immune system are reviewed. Finally, a brief outlook on the trajectory of these systems and how they may be improved to address unsolved challenges in cancer, infectious diseases, and autoimmunity is presented.

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Section: Nanoscale Materials For Immunotherapymentioning

confidence: 99%

Section: Cell-derived Nanovesicles With Liquid Coresmentioning

confidence: 99%

Materials for Immunotherapy

et al. 2019

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“…T cells derived from mice vaccinated with the formulation produced a robust immune response against the parent B16‐OVA cells as indicated by IL‐2 production. The introduction of polyethylene glycol (PEG) onto cancer cell nanovesicles loaded with adjuvant has better enabled the in vivo use of this platform . Cultured B16‐OVA cells were lysed by freeze–thawing and then sonicated to form nanovesicles.…”

Section: Biomimetic Anticancer Nanovaccinesmentioning

confidence: 99%

“…The introduction of polyethylene glycol (PEG) onto cancer cell nanovesicles loaded with adjuvant has better enabled the in vivo use of this platform. [201] Cultured B16-OVA cells were lysed by freezethawing and then sonicated to form nanovesicles. To enhance immunogenicity, the nanovesicles were loaded with cholesterol-conjugated CpG, then finally PEGylated using a lipid-PEG conjugate to improve transport through the lymphatic system.…”

Section: Whole Cell Vaccinationsmentioning

confidence: 99%

Biomimetic Nanotechnology toward Personalized Vaccines

et al. 2019

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While traditional approaches for disease management in the era of modern medicine have saved countless lives and enhanced patient well‐being, it is clear that there is significant room to improve upon the current status quo. For infectious diseases, the steady rise of antibiotic resistance has resulted in super pathogens that do not respond to most approved drugs. In the field of cancer treatment, the idea of a cure‐all silver bullet has long been abandoned. As a result of the challenges facing current treatment and prevention paradigms in the clinic, there is an increasing push for personalized therapeutics, where plans for medical care are established on a patient‐by‐patient basis. Along these lines, vaccines, both against bacteria and tumors, are a clinical modality that could benefit significantly from personalization. Effective vaccination strategies could help to address many challenging disease conditions, but current vaccines are limited by factors such as a lack of potency and antigenic breadth. Recently, researchers have turned toward the use of biomimetic nanotechnology as a means of addressing these hurdles. Recent progress in the development of biomimetic nanovaccines for antibacterial and anticancer applications is discussed, with an emphasis on their potential for personalized medicine.

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“…In this study, we examined cell‐derived vesicles for antigen delivery to promote antigen‐specific T cell responses. Utilizing cell membrane preparation technologies that we and others have reported, we generated dendritic cell membrane vesicles (DC‐MVs) from preactivated antigen‐presenting cells (APCs) ( Figure A). Here, we show that DC‐MVs can be effectively loaded with antigen peptides and promote activation of antigen‐specific T cells in vitro.…”

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confidence: 99%

Dendritic Cell Membrane Vesicles for Activation and Maintenance of Antigen‐Specific T Cells

Ochyl

Moon

2018

Adv Healthcare Materials

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depots at the site of administration leading to diminished potency. [7] In this study, we examined cell-derived vesicles for antigen delivery to promote antigen-specific T cell responses. Utilizing cell membrane preparation technologies that we and others have reported, [8][9][10] we generated dendritic cell membrane vesicles (DC-MVs) from preactivated antigen-presenting cells (APCs) ( Figure 1A). Here, we show that DC-MVs can be effectively loaded with antigen peptides and promote activation of antigen-specific T cells in vitro. We also demonstrate their potency to expand adoptively transferred T cells in vivo. Our results suggest that DC-MVs are a promising platform for augmenting adoptive T cell therapy and improving peptide-based cancer vaccination.To generate DC-MVs, we first obtained DCs from bone marrow of C57BL/6 mice with the use of granulocyte-macrophage colony-stimulating factor. [11] Immature bone marrow-derived dendritic cells (BMDCs) were lysed by freeze-thaw cycles and mild probe-tip sonication. After removing large debris and organelles via centrifugation, the resulting lysate samples were incubated with 20 × 10 −3 m CaCl 2 for 1 h to promote fusion and aggregation of cellular membranes, which allowed for isolation of DC-MVs with table-top centrifugation. We sought to preactivate DCs before generating DC-MVs and studied their impact on the subsequent T cell cross-priming. Specifically, we preactivated BMDCs with monophosphoryl lipid A (MPLA), a FDA-approved immunostimulatory Toll-like receptor 4 agonist. [12,13] We first confirmed upregulation of costimulatory markers, including CD80 and CD86, in whole cell lysate of MPLA-treated DCs by Western blotting (Figure 1B). Immature DCs without any MPLA treatment (NO TX) exhibited minimal expression of CD80 or CD86. By contrast, pretreatment of DCs with MPLA increased the expression levels of costimulatory markers, in particular, CD86, on DC-MVs regardless whether BMDCs were harvested from culture dishes either by Accutase treatment and a cell scraper (MPLA) or by pipetting (MPLA-S) ( Figure 1B). Based on these results and high yield of total protein (80%) from the Accutase-based harvest, we proceeded with this method for the source for MPLA-activated DC-MVs, which is henceforth termed (MPLA)DC-MVs. Dynamic light scattering analysis indicated that (MPLA)DC-MVs had an average hydrodynamic size of 130 ± 4 nm and a polydispersity index of 0.17 ± 0.01.Next, we examined the ability of DC-MVs to present antigen peptides directly to T cells and promote their activation and Cell membranes have recently gained attention as a promising drug delivery system. Here, dendritic cell membrane vesicles (DC-MVs) are examined as a platform to promote T cell responses. Nanosized DC-MVs are derived from DCs pretreated with monophosphoryl lipid A (MPLA), a FDA-approved immunostimulatory adjuvant. These "mature" DC-MVs activate DCs in vitro and increase their expression of costimulatory markers. DC-MVs also promote cross-priming of antigen-specific T cells in vitro, increasing ...

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PEGylated tumor cell membrane vesicles as a new vaccine platform for cancer immunotherapy

Cited by 85 publications

References 34 publications

Materials for Immunotherapy

Materials for Immunotherapy

Biomimetic Nanotechnology toward Personalized Vaccines

Dendritic Cell Membrane Vesicles for Activation and Maintenance of Antigen‐Specific T Cells

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