Application of Surface-Linked Liposomal Antigens to the Development of Vaccines That Induce Both Humoral and Cellular Immunity

Uchida, Tetsuya; Taneichi, Maiko

doi:10.7883/yoken.67.235

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…In this assay, DC2.4 or BMDCs were incubated with soluble OVA or liposomal OVA (complexed with Lipofectamine 2000) for 20 hours and cocultured with B3Z (a CD8 T cell hybridoma specifically recognize OVA epitope) for 24 hours, then the IL-2 promoter-driven LacZ activity in T cells was measured to quantify IL-2 expression. Consistent with the previous report, 17 liposomal OVA-primed, but not soluble OVA-primed DCs, significantly increased IL-2 reporter activity in T cells ( online supplemental figure 1A ). We next pretreated DC2.4 cells in 96 wells with a panel of small molecule inhibitors and FDA-approved drugs targeting different proteins with known or potential immune-modulating functions, and then tested their impacts on antigen presentation ability of DCs ( online supplemental table 2 ).…”

Section: Resultssupporting

confidence: 92%

Modulation of lactate-lysosome axis in dendritic cells by clotrimazole potentiates antitumor immunity

Wang

et al. 2021

J Immunother Cancer

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BackgroundDendritic cells (DCs) play a critical role in antitumor immunity, but the therapeutic efficacy of DC-mediated cancer vaccine remains low, partly due to unsustainable DC function in tumor antigen presentation. Thus, identifying drugs that could enhance DC-based antitumor immunity and uncovering the underlying mechanism may provide new therapeutic options for cancer immunotherapy.MethodsIn vitro antigen presentation assay was used for DC-modulating drug screening. The function of DC and T cells was measured by flow cytometry, ELISA, or qPCR. B16, MC38, CT26 tumor models and C57BL/6, Balb/c, nude, and Batf3−/− mice were used to analyze the in vivo therapy efficacy and impact on tumor immune microenvironment by clotrimazole treatment.ResultsBy screening a group of small molecule inhibitors and the US Food and Drug Administration (FDA)-approved drugs, we identified that clotrimazole, an antifungal drug, could promote DC-mediated antigen presentation and enhance T cell response. Mechanistically, clotrimazole acted on hexokinase 2 to regulate lactate metabolic production and enhanced the lysosome pathway and Chop expression in DCs subsequently induced DC maturation and T cell activation. Importantly, in vivo clotrimazole administration induced intratumor immune infiltration and inhibited tumor growth depending on both DCs and CD8+ T cells and potentiated the antitumor efficacy of anti-PD1 antibody.ConclusionsOur findings showed that clotrimazole could trigger DC activation via the lactate-lysosome axis to promote antigen cross-presentation and could be used as a potential combination therapy approach to improving the therapeutic efficacy of anti-PD1 immunotherapy.

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Section: Resultssupporting

confidence: 92%

Modulation of lactate-lysosome axis in dendritic cells by clotrimazole potentiates antitumor immunity

Wang

et al. 2021

J Immunother Cancer

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“…[10] For example, among various vaccine carriers, this strategy has been developed to chemically conjugate antigens to the surface of the modified liposomes, resulting in the stabilization of the antigens on their surface mimicking the native pathogens. [12] There are covalent and non-covalent interactions between nanoparticles (NPs) and proteins. [13] Protein-NPs can covalently conjugated by the direct interaction of protein residues with nanoparticles, in which the stability and irreversibility of protein-NPs complex makes this technique suitable for biological media containing other interfering species.…”

Section: Introductionmentioning

confidence: 99%

“…The use of metal‐inserted porphyrin‐lipid in the modified porphysomes can also change its role from a simple nanocarrier to an advanced imaging or stabilized platform for improving protein immunogens [10] . For example, among various vaccine carriers, this strategy has been developed to chemically conjugate antigens to the surface of the modified liposomes, resulting in the stabilization of the antigens on their surface mimicking the native pathogens [12] . There are covalent and non‐covalent interactions between nanoparticles (NPs) and proteins [13] .…”

Section: Introductionmentioning

confidence: 99%

Porphysome Engineered With Specific Protein Binding Sites as a Multimodal Theranostic Nanocarrier for Targeted Protein Delivery

Ayyari,

Vaezi,

Ashin

et al. 2024

Chemistry & Biodiversity

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The immobilization of proteins on the surface of carriers is challenging due to the loss of protein structure and function in this process. Here, we report the development of the protein immobilization on the surface of the metallated‐porphyrin complex in the porphysome nanocarrier. The conjugated Ni‐porphyrin to fatty acid (as a tail) has been synthesized and independently placed at the depth of the bilayer center of Dipalmitoylphosphatidylcholine (DPPC) in which the Ni‐porphyrin was at the polar region of the membrane and is thus superficial. This porphysome (DPPC: Ni‐porphyrin, 4:1 mole ratio) was formed by supramolecular self‐assembly with a diameter of 173±7 nm and zeta potential ‐8.5±3.4 mv, which exhibited no significant toxicity at the experimental concentrations and acceptable cellular uptake on MCF‐7 cells. The physicochemical properties and specific protein binding sites of the firefly luciferase as a model protein into the porphysome (1:2 mole ratio) show the conjugation efficiency about 80% and the conformation of protein was completely maintained. Furthermore, bioluminescence assay and SDS‐PAGE confirmed the preservation of protein function. The stabilized platform of porphyrin‐lipid structure can potentially improve the efficacy of protein functionality for a particular display, shifting porphysomes from a simple carrier to a therapeutic agent.

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Liposome engraftment and antigen combination potentiate the immune response towards conserved epitopes of the malaria vaccine candidate MSP2

Das

Price

Gosling

et al. 2021

Vaccine

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Application of Surface-Linked Liposomal Antigens to the Development of Vaccines That Induce Both Humoral and Cellular Immunity

Cited by 4 publications

References 32 publications

Modulation of lactate-lysosome axis in dendritic cells by clotrimazole potentiates antitumor immunity

Modulation of lactate-lysosome axis in dendritic cells by clotrimazole potentiates antitumor immunity

Porphysome Engineered With Specific Protein Binding Sites as a Multimodal Theranostic Nanocarrier for Targeted Protein Delivery

Liposome engraftment and antigen combination potentiate the immune response towards conserved epitopes of the malaria vaccine candidate MSP2

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