Delivery of TLR7 agonist to monocytes and dendritic cells by DCIR targeted liposomes induces robust production of anti-cancer cytokines

Klauber, Thomas Christopher Bogh; Laursen, Janne Marie; Zucker, Daniel; Brix, Susanne; Jensen, Simon Skøde; Andresen, Thomas Lars

doi:10.1016/j.actbio.2017.01.072

Cited by 34 publications

(15 citation statements)

References 80 publications

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“…Conclusively, DCIR deficiency seems to support antiviral immune responses of C57BL/6 mice during the initial phase of TMEV infection and to reduce virus-induced neuropathology. Previous studies highlight the potential of DCIR for cell specific targeting and immune modulation 51 , 52 , 76 . Thus, this CLR represents a potential target for intervention strategies to selectively enhance protective immunity in neurotropic virus infection.…”

Section: Discussionmentioning

confidence: 99%

C-type lectin receptor DCIR contributes to hippocampal injury in acute neurotropic virus infection

Stoff¹,

Ebbecke

Ciurkiewicz³

et al. 2021

Sci Rep

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Neurotropic viruses target the brain and contribute to neurologic diseases. C-type lectin receptors (CLRs) are pattern recognition receptors that recognize carbohydrate structures on endogenous molecules and pathogens. The myeloid CLR dendritic cell immunoreceptor (DCIR) is expressed by antigen presenting cells and mediates inhibitory intracellular signalling. To investigate the effect of DCIR on neurotropic virus infection, mice were infected experimentally with Theiler’s murine encephalomyelitis virus (TMEV). Brain tissue of TMEV-infected C57BL/6 mice and DCIR−/− mice were analysed by histology, immunohistochemistry and RT-qPCR, and spleen tissue by flow cytometry. To determine the impact of DCIR deficiency on T cell responses upon TMEV infection in vitro, antigen presentation assays were utilised. Genetic DCIR ablation in C57BL/6 mice was associated with an ameliorated hippocampal integrity together with reduced cerebral cytokine responses and reduced TMEV loads in the brain. Additionally, absence of DCIR favoured increased peripheral cytotoxic CD8+ T cell responses following TMEV infection. Co-culture experiments revealed that DCIR deficiency enhances the activation of antigen-specific CD8+ T cells by virus-exposed dendritic cells (DCs), indicated by increased release of interleukin-2 and interferon-γ. Results suggest that DCIR deficiency has a supportive influence on antiviral immune mechanisms, facilitating virus control in the brain and ameliorates neuropathology during acute neurotropic virus infection.

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Section: Discussionmentioning

confidence: 99%

C-type lectin receptor DCIR contributes to hippocampal injury in acute neurotropic virus infection

Stoff¹,

Ebbecke

Ciurkiewicz³

et al. 2021

Sci Rep

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“…Further investigators formulated an immune-stimulating TLR7 agonist (TMX-202) in the liposomes and examined its immune activating potential in immune cells that included blood-derived monocytes, myeloid dendritic cells (DCs), and plasmacytoid DCs. These cells exhibited potent TLR7-specific secretion of some cytokines that have anti-cancer effects (IL-12p70, IFN-α, and IFN-γ) [20]. Based on these findings, two formulations of TLR7 agonists (TMX-101 and TMX-202) were investigated to determine their therapy potential for urothelial carcinoma in an orthotopic bladder cancer rat model.…”

Section: Discussionmentioning

confidence: 99%

Serum level and single-nucleotide polymorphisms of toll-like receptor-7 among urinary bladder cancer Iraqi patients

Al-Humairi

Al-Musawi

Ad’hiah

2019

Egypt J Med Hum Genet

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Background: Toll-like receptor 7 (TLR7), a member of TLR family, plays a pivotal role in pathogenesis of different malignancies. Among these is urinary bladder cancer (UBC), which has not been extensively studied. Therefore, it was aimed to determine TLR7 serum level in UBC patients and evaluate its association with some demographic and clinicopathological characteristics. In addition, four TLR7 single-nucleotide polymorphisms (SNPs: rs179018, rs179019, rs179020, and rs179021) were investigated to determine their susceptibility role in UBC and inspect SNP's impact on TLR7 level. Sixty-six UBC Iraqi patients were enrolled in this case-control study. Two control samples were also involved, 40 urinary tract infection (UTI) patients, and 48 healthy control subjects. Results: Male gender, older age, and cigarette-smoking are risk factors for UBC. TLR7 level showed a significant decreased median in UBC patients compared to UTI patients or control (1.4 vs. 8.1 and 9.5 ng/ml, respectively; p < 0.001). The decrease was more pronounced in males, age group ≥ 48 years, cigarette-smokers, alcohol non-consumers, clinical stages I-II, and superficial tumor, as well as patients with family history of cancer and untreated patients. Mitomycin C and Bacillus Calmette-Guérin therapies tended to increase TLR7 level. Among the four investigated SNPs, only rs179019 C allele showed significantly uncorrected increased frequency in UBC males compared to control males (p = 0.038), while among UTI females, C allele frequency maintained a significantly corrected decreased frequency compared to control females (p = 0.005). Some SNPs influenced serum level of TLR7, but a significant impact was recorded for rs179019 in UTI females (p = 0.006). Conclusions: Downregulation of TLR7 is suggested to have a role in etiology and pathogenesis of UBC, especially the male, elderly and smoker patients. Mitomycin C and Bacillus Calmette-Guérin may enhance TLR7 production in the blood of UBC patients. TLR7 SNPs are suggested to influence susceptibility to develop UBC, and their potential in impacting TLR7 serum level is augmented.

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“…They demonstrated a significant increase in IL-12p40 secretion from RAW264.7 macrophages and specific binding to CD20 + CD19 + B cells in vitro [ 284 ]. Andresen and colleagues used maleimide functionalized liposomes attached to murine anti-human DCIR (dendritic cell immunoreceptor) monoclonal antibodies (IgG 1 specific for a nonhuman epitope) via Traut’s reagent (i.e., 2-iminothiolane) [ 285 ]. They observed preferential uptake of the nanoparticles by monocytes and mDCs when evaluated in vitro in PBMCs and significantly enhanced secretion of inflammatory cytokines such as IL-6 and TNF-α.…”

Section: Bioconjugation and Other Delivery Strategiesmentioning

confidence: 99%

Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants

Bhagchandani

Johnson

Irvine

2021

Advanced Drug Delivery Reviews

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Delivery of TLR7 agonist to monocytes and dendritic cells by DCIR targeted liposomes induces robust production of anti-cancer cytokines

Cited by 34 publications

References 80 publications

C-type lectin receptor DCIR contributes to hippocampal injury in acute neurotropic virus infection

C-type lectin receptor DCIR contributes to hippocampal injury in acute neurotropic virus infection

Serum level and single-nucleotide polymorphisms of toll-like receptor-7 among urinary bladder cancer Iraqi patients

Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants

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