pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity

Yuba, Eiji; Sakaguchi, Naoki; Kanda, Yuhei; Miyazaki, Maiko; Koiwai, Kazunori

doi:10.3390/vaccines5040041

Cited by 16 publications

(8 citation statements)

References 39 publications

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“…42 Indeed, increased colocalization of OVA with MHC I exhibiting a diffuse cytosolic-like staining was observed in BMDCs cotreated with OVA plus βγ-CAT ( Figure 2D), and similar results has been reported that the cytoplasmic delivery of antigen may induce cross-presentation to activate antigenspecific cellular immunity. 43 Thus, our results suggested that βγ-CAT might induce the release of endocytic OVA into the cytoplasm to trigger the MHC I processing pathway via pore formation and neutralization of intracellular acidification. In addition, we further assessed the colocalization of OVA and MHC II in BMDCs treated with βγ-CAT.…”

Section: βγ-Cat Increases Antigen Presentation Capacity By Bmdcs VImentioning

confidence: 60%

A secreted pore‐forming protein modulates cellular endolysosomes to augment antigen presentation

Deng

Liu

et al. 2020

FASEB j.

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Bacterial pore‐forming toxin aerolysin‐like proteins are widely distributed in animals and plants. Emerging evidence supports their roles in host innate immunity, but their direct actions in adaptive immunity remain elusive. In this study, we found that βγ‐CAT, an aerolysin‐like protein and trefoil factor complex identified in the frog Bombina maxima, modulated several steps of endocytic pathways during dendritic cell antigen presentation. The protein augmented the antigen uptake of dendritic cells and actively neutralized the acidification of cellular endocytic organelles to favor antigen presentation. In addition, the release of functional exosome‐like extracellular vesicles was largely enhanced in the presence of βγ‐CAT. The cellular action of βγ‐CAT increased the number of major histocompatibility complex (MHC) I‐ovalbumin and MHC II molecules on dendritic cell surfaces and the released exosome‐like extracellular vesicles. An enhanced antigen presentation capacity of dendritic cell for priming of naive T cells was detected in the presence of βγ‐CAT. Collectively, these effects led to strong cytotoxic T lymphocyte responses and antigen‐specific antibody responses. Our findings provide evidence that a vertebrate‐secreted pore‐forming protein can augment antigen presentation by directly modulating cellular endocytic and exocytic pathways, leading to robust activation of adaptive immunity.

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Section: βγ-Cat Increases Antigen Presentation Capacity By Bmdcs VImentioning

confidence: 60%

A secreted pore‐forming protein modulates cellular endolysosomes to augment antigen presentation

Deng

Liu

et al. 2020

FASEB j.

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“…More advanced strategies to facilitate immunogenic delivery into the cytosol depend on the lower pH of the early/late endosome . For example, CaP skeleton as a shell protects CpG oligonucleotides from clearance by macropinocytosis and responds to acidic organelle environment for on‐command release in cytosol .…”

Section: Nanomaterials For Target Deliverymentioning

confidence: 99%

“…[129] More advanced strategies to facilitate immunogenic delivery into the cytosol depend on the lower pH of the early/late endosome. [130][131][132][133][134] For example, CaP skeleton as a shell protects CpG oligonucleotides from clearance by macropinocytosis and responds to acidic organelle environment for on-command release in cytosol. [135] An alternative method involves cell-penetrating peptides on the nanoparticle surface, which Small 2019, 15,1900262 Reproduced with permission.…”

Section: Nanomaterials Promote Intracellular Delivery Of Immunotherapmentioning

confidence: 99%

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Liu

Zhang

2019

Small

124

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Cancer immunotherapy is a promising cancer terminator by directing the patient's own immune system in the fight against this challenging disorder. Despite the monumental therapeutic potential of several immunotherapy strategies in clinical applications, the efficacious responses of a wide range of immunotherapeutic agents are limited in virtue of their inadequate accumulation in the tumor tissue and fatal side effects. In the last decades, increasing evidences disclose that nanotechnology acts as an appealing solution to address these technical barriers via conferring rational physicochemical properties to nanomaterials. In this Review, an imperative emphasis will be drawn from the current understanding of the effect of a nanosystem's structure characteristics (e.g., size, shape, surface charge, elasticity) and its chemical modification on its transport and biodistribution behavior. Subsequently, rapid‐moving advances of nanoparticle‐based cancer immunotherapies are summarized from traditional vaccine strategies to recent novel approaches, including delivery of immunotherapeutics (such as whole cancer cell vaccines, immune checkpoint blockade, and immunogenic cell death) and engineered immune cells, to regulate tumor microenvironment and activate cellular immunity. The future prospects may involve in the rational combination of a few immunotherapies for more efficient cancer inhibition and elimination.

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“…[ 69 ] For example, PEG can be utilized as functional ligands to enhance the flexibility of dendrimers, so as to improve the efficiency of delivering genes to immune cells. [ 70 ] More interestingly, dendrimers can recognize DCs through multiple receptors (i.e., C‐type polylectin receptor CD205, mannose receptor (MR or CD206), dendritic cell‐specific intercellular adhesion molecule 3 grabbing nonintegrin or DC‐SIGN, as well as lectin 1/2) and further internalize DCs to promote further immune response ( Figure a). [ 71 ]…”

Section: Structural Designs Of Polymeric Nonviral Gene Delivery Systemsmentioning

confidence: 99%

Polymeric Nonviral Gene Delivery Systems for Cancer Immunotherapy

Cai

et al. 2020

Advanced Therapeutics

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Unlike viral vectors with their undesired safety or immunogenicity concerns, biocompatible polymeric nonviral vectors as gene delivery systems are more promising in gene or cell therapy. Evidence has demonstrated that the rational design of polymeric nonviral gene vectors with optimal structure, charge density, biocompatibility, and stimulus responsiveness can deliver therapeutic genes or gene vaccines (in terms of deoxyribonucleic acid DNA or ribonucleic acid RNA) into tumor‐associated immunocytes (i.e., macrophages, T cells, or dendritic cells) in an effective and controllable manner for enhanced cancer immunotherapy. However, a timely and systematic summary of this subject is lacking. This review presents an overview of polymeric nonviral carriers with immune cell transfection ability and their potential applications in cancer immunotherapy; it also provides a tutorial for designing polymeric immune‐cell genetic modification vector, although there are still few vectors in the product pipeline. With the rapid growth of immunotherapy in cancer treatment and knowledge accumulation in vector structure design, polymeric nonviral gene delivery systems may provide new hope for tumor therapy.

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pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity

Cited by 16 publications

References 39 publications

A secreted pore‐forming protein modulates cellular endolysosomes to augment antigen presentation

A secreted pore‐forming protein modulates cellular endolysosomes to augment antigen presentation

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Polymeric Nonviral Gene Delivery Systems for Cancer Immunotherapy

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