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https://www.readbyqxmd.com/read/29157965/polymer-based-nanoparticles-loaded-with-a-tlr7-ligand-to-target-the-lymph-node-for-immunostimulation
#1
Jérôme Widmer, Cédric Thauvin, Inès Mottas, Van N'guyen, Florence Delie, Eric Allémann, Carole Bourquin
Small-molecule agonists for the Toll-like receptors (TLR) 7 and 8 are effective for the immunotherapy of skin cancer when used as topical agents. Their systemic use has however been largely unsuccessful due to dose-limiting toxicity. We propose a polymer-based nanodelivery system to target resiquimod, a TLR7 ligand, to the lymph node in order to focus the immunostimulatory activity and to prevent a generalized inflammatory response. We demonstrate successful encapsulation of resiquimod in methoxypoly(ethylene glycol)-b-poly(DL-lactic acid) (mPEG-PLA) and mixed poly(DL-lactic-co-glycolic acid) (PLGA)/mPEG-PLA nanoparticles...
November 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28955328/co-delivery-of-dual-toll-like-receptor-agonists-and-antigen-in-poly-lactic-co-glycolic-acid-polyethylenimine-cationic-hybrid-nanoparticles-promote-efficient-in-vivo-immune-responses
#2
Mahboubeh Ebrahimian, Maryam Hashemi, Mohsen Maleki, Gholamreza Hashemitabar, Khalil Abnous, Mohammad Ramezani, Alireza Haghparast
Strategies to design delivery vehicles are critical in modern vaccine-adjuvant development. Nanoparticles (NPs) encapsulating antigen(s) and adjuvant(s) are promising vehicles to deliver antigen(s) and adjuvant(s) to antigen-presenting cells (APCs), allowing optimal immune responses against a specific pathogen. In this study, we developed a novel adjuvant delivery approach for induction of efficient in vivo immune responses. Polyethylenimine (PEI) was physically conjugated to poly(lactic-co-glycolic) acid (PLGA) to form PLGA/PEI NPs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28910320/differential-gene-expression-following-tlr-stimulation-in-rag1-mutant-zebrafish-tissues-and-morphological-descriptions-of-lymphocyte-like-cell-populations
#3
Preeti J Muire, Larry A Hanson, Robert Wills, Lora Petrie-Hanson
In the absence of lymphocytes, rag1-/- mutant zebrafish develop protective immunity to bacteria. In mammals, induction of protection by innate immunity can be mediated by macrophages or natural killer (NK) cells. To elucidate potential responsive cell populations, we morphologically characterized lymphocyte-like cells (LLCs) from liver, spleen and kidney hematopoietic tissues. In fish, these cells include NK cells and Non-specific cytotoxic cells (NCCs). We also evaluated the transcriptional expression response of select genes that are important indicators of NK and macrophage activation after exposure to specific TLR ligands...
2017: PloS One
https://www.readbyqxmd.com/read/28890720/porcine-b-cell-subset-responses-to-toll-like-receptor-ligands
#4
Roman Othmar Braun, Sylvie Python, Artur Summerfield
Toll-like receptors (TLR) triggering of B cells are known to promote B cell expansion, differentiation of B cells into antibody-producing and memory cells, but the TLR responses of porcine B cells is poorly characterized. Therefore, this study investigated the response pattern of porcine B cell subsets to a large collection of TLR ligands and demonstrates that the TLR2 ligand Pam3Cys-SK4 and the TLR7/8 ligands gardiquimod and resiquimod are particularly efficient at inducing proliferation, CD25 and CCR7. This activation was also determined in B-cell subpopulations including a CD21(+)IgM(+) subset, an IgG(+) subset and two putative B1-like subsets, defined as CD21(-)IgM(high)CD11R1(+)CD11c(+)CD14(+) and CD21(-)IgM(high) CD11R1(-)CD11c(+)CD14(-) B cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28881713/therapeutic-vaccine-to-cure-large-mouse-hepatocellular-carcinomas
#5
Zhen Han, De Yang, Anna Trivett, Joost J Oppenheim
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with limited therapeutic options. Here we report the development of a therapeutic vaccination regimen (shortened as 'TheraVac') consisting of intratumoral delivery of high-mobility group nucleosome-binding protein 1 (HMGN1), R848/resiquimod, and one of the checkpoint inhibitors (e.g. anti-CTLA4, anti-PD-L1, or low dose of Cytoxan). C57BL/6 mice harboring large (approximately 1 cm in diameter) established subcutaneous Hepa1-6 hepatomas were cured by intratumoral injections of TheraVac and became tumor-free long-term survivors...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28869081/differential-regulation-of-il-23-production-in-m1-macrophages-by-tir8-sigirr-through-tlr4-or-tlr7-8-mediated-signaling
#6
Rui Yamaguchi, Arisa Sakamoto, Takatoshi Yamamoto, Shinji Narahara, Hiroyuki Sugiuchi, Yasuo Yamaguchi
Cross-talks between toll-like receptors (TLRs) including various negative regulatory mechanisms are many unknown. We investigated the differential mechanism of IL-23 production in M1 macrophages by single immunoglobulin interleukin-1 receptor-related (SIGIRR) molecule through TLR4 or TLR7/8. IL-12p40 production by M1 macrophages pretreated with human neutrophil elastase (HNE) was synergistically enhanced IL-12p40, but not IL-23 production, after exposure to lipopolysaccharide (LPS). LPS (a TLR4 agonist) induced a slight increase of IL-23 production, while Resiquimod (a TLR7/8 agonist) significantly enhanced IL-23 production...
August 28, 2017: Cytokine
https://www.readbyqxmd.com/read/28743833/therapeutic-vaccine-to-cure-large-mouse-hepatocellular-carcinomas
#7
Zhen Han, De Yang, Anna Trivett, Joost J Oppenheim
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with limited therapeutic options. Here we report the development of a therapeutic vaccination regimen (shortened as 'TheraVac') consisting of intratumoral delivery of high-mobility group nucleosome-binding protein 1 (HMGN1), R848/resiquimod, and one of the checkpoint inhibitors (e.g. anti-CTLA4, anti-PD-L1, or low dose of Cytoxan). C57BL/6 mice harboring large (approximately 1 cm in diameter) established subcutaneous Hepa1-6 hepatomas were cured by intratumoral injections of TheraVac and became tumor-free long-term survivors...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28648870/tlr7-and-tlr8-agonist-resiquimod-r848-differently-regulates-mif-expression-in-cells-and-organs
#8
Yao Mawulikplimi Adzavon, Pengxiang Zhao, Baobei Lv, Mengyu Liu, Xin Zhang, Fei Xie, Linqi Yang, Lei Shang, Mingzi Zhang, Qinjian Li, Xuemei Ma
Since its first description in 1966, macrophage migration inhibitory factor (MIF) was found to play a critical role in inflammatory and immune responses as well as in disease pathogenesis especially in tumor pathogenesis and cancer progression. MIF is expressed in different cell types and is associated with many disease severity and tumor pathogenesis. Here, we investigated the influence of TLR7 and TLR8 agonist resiquimod (R848), an immune response inducer used as a prophylactic agent for several infectious diseases as well as anticancer agents and vaccine adjuvant on MIF expression in cells and organs...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28620298/anti-tumor-activity-of-toll-like-receptor-7-agonists
#9
REVIEW
Huju Chi, Chunman Li, Flora Sha Zhao, Li Zhang, Tzi Bun Ng, Guangyi Jin, Ou Sha
Toll-like receptors (TLRs) are a class of pattern recognition receptors that play a bridging role in innate immunity and adaptive immunity. The activated TLRs not only induce inflammatory responses, but also elicit the development of antigen specific immunity. TLR7, a member of TLR family, is an intracellular receptor expressed on the membrane of endosomes. TLR7 can be triggered not only by ssRNA during viral infections, but also by immune modifiers that share a similar structure to nucleosides. Its powerful immune stimulatory action can be potentially used in the anti-tumor therapy...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28582454/insights-on-the-mechanism-of-action-of-immunostimulants-in-relation-to-their-pharmacological-potency-the-effects-of-imidazoquinolines-on-tlr8
#10
Carlos Kubli-Garfias, Ricardo Vázquez-Ramírez, Cynthia Trejo-Muñoz, Arturo Berber
Imidazoquinolines are powerful immunostimulants (IMMS) that function through Toll-like receptors, particularly TLR7 and TLR8. In addition to enhancing the immune response, IMMS also function as antineoplastic drugs and vaccine adjuvants. These small compounds display almost the same molecular structure, except in some cases in which atom in position 1 varies and changes the imidazole characteristics. A variable acyclic side chain is also always attached at atom in position 2, while another chain may be attached at atom in position 1...
2017: PloS One
https://www.readbyqxmd.com/read/28540671/multidisciplinary-management-of-mycosis-fungoides-s%C3%A3-zary-syndrome
#11
REVIEW
Sara Berg, Jennifer Villasenor-Park, Paul Haun, Ellen J Kim
PURPOSE OF REVIEW: Diagnosis and management of mycosis fungoides and Sézary syndrome (MF/SS) require accurate clinicopathological correlation and a multidisciplinary approach. We reviewed major advances in the field regarding diagnostic and prognostic tools as well as skin-directed therapies (SDTs) and systemic agents for MF/SS published in the past 2 years. RECENT FINDINGS: Improved technology (T-cell receptor high-throughput sequencing) and increased multicenter collaboration (Cutaneous Lymphoma International Consortium) have led to diagnostic/prognostic advances...
June 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28502294/-resiquimod-r848-has-more-stronger-immune-adjuvantivity-than-other-tested-tlr-agonists
#12
Yuan Shen, Menghua Zeng, Feng Qiu, Hua Tang
Objective To compare and characterize the Th1 immune responses induced by the most commonly used commercial Toll-like receptor (TLR) agonists through in vivo and ex vivo experiments. Methods The concentrations of IL-12 were tested by ELISA after mouse dendritic cells (DCs) in vitro were stimulated by one of tested TLR agonists, including poly(I:C), monophosphoryl lipid A (MPLA), resiquimod (R848), cytosine polyguanine-C (CpG-C). The changes in percentage and phenotype of DCs, NK cells and effector T cells in the draining lymph nodes were analyzed by flow cytometry after BALB/c mice were immunized with ovalbumin (OVA) mixed with selected TLR agonist...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28250051/systemic-autoimmunity-induced-by-the-tlr7-8-agonist-resiquimod-causes-myocarditis-and-dilated-cardiomyopathy-in-a-new-mouse-model-of-autoimmune-heart-disease
#13
Muneer G Hasham, Nicoleta Baxan, Daniel J Stuckey, Jane Branca, Bryant Perkins, Oliver Dent, Ted Duffy, Tolani S Hameed, Sarah E Stella, Mohammed Bellahcene, Michael D Schneider, Sian E Harding, Nadia Rosenthal, Susanne Sattler
Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod...
March 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27999739/tlr7-based-cancer-immunotherapy-decreases-intratumoral-myeloid-derived-suppressor-cells-and-blocks-their-immunosuppressive-function
#14
Thibaud Spinetti, Lorenzo Spagnuolo, Inès Mottas, Chiara Secondini, Marina Treinies, Curzio Rüegg, Christian Hotz, Carole Bourquin
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with the capacity to inhibit immunological responses. During cancer progression, MDSC are recruited to the tumor sites and secondary lymphoid organs, leading to the suppression of the antitumor function of NK and T cells. Here, we show that the TLR7/8 agonist resiquimod (R848) has a direct effect on MDSC populations in tumor-bearing mice. Systemic application of R848 led to a rapid reduction in both intratumoral and circulating MDSC...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27997339/toll-like-receptor-3-adjuvant-in-combination-with-virus-like-particles-elicit-a-humoral-response-against-hiv
#15
Ethan Poteet, Phoebe Lewis, Changyi Chen, Sam On Ho, Thai Do, SuMing Chiang, Celia Labranche, David Montefiori, Gary Fujii, Qizhi Yao
Human Immunodeficiency Virus (HIV) Virus-Like Particles (VLPs) composed of HIVIIIB Gag and HIVBaL gp120/gp41 envelope are a pseudovirion vaccine capable of presenting antigens in their native conformations. To enhance the immunogenicity of the HIV Env antigen, VLPs were coupled to VesiVax Conjugatable Adjuvant Lipid Vesicles (CALV) containing one of four toll-like-receptor (TLR) ligands, each activating a receptor with distinct cellular localization and downstream pathways. C57BL/6 mice were vaccinated by intranasal prime followed by two sub-cheek boosts and their sera immunoglobulin and neutralizing potency were measured over a duration of 3months after vaccination...
November 21, 2016: Vaccine
https://www.readbyqxmd.com/read/27995135/trim25-identification-in-the-chinese-goose-gene-structure-tissue-expression-profiles-and-antiviral-immune-responses-in-vivo-and-in-vitro
#16
Yunan Wei, Hao Zhou, Anqi Wang, Lipei Sun, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Qiao Yang, Ying Wu, Kunfeng Sun, Xiaoyue Chen, Anchun Cheng, Shun Chen
The retinoic acid-inducible gene I (RIG-I) and the RIG-I-like receptor (RLR) protein play a critical role in the interferon (IFN) response during RNA virus infection. The tripartite motif containing 25 proteins (TRIM25) was reported to modify caspase activation and RIG-I recruitment domains (CARDs) via ubiquitin. These modifications allow TRIM25 to interact with mitochondrial antiviral signaling molecules (MAVs) and form CARD-CARD tetramers. Goose TRIM25 was cloned from gosling lungs, which possess a 1662 bp open reading flame (ORF)...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27974697/surrogate-in-vitro-activation-of-innate-immunity-synergizes-with-interleukin-7-to-unleash-rapid-antigen-driven-outgrowth-of-cd4-and-cd8-human-peripheral-blood-t-cells-naturally-recognizing-muc1-her2-neu-and-other-tumor-associated-antigens
#17
Latha B Pathangey, Dustin B McCurry, Sandra J Gendler, Ana L Dominguez, Jessica E Gorman, Girish Pathangey, Laurie A Mihalik, Yushe Dang, Mary L Disis, Peter A Cohen
Effective adoptive immunotherapy has proved elusive for many types of human cancer, often due to difficulties achieving robust expansion of natural tumor-specific T-cells from peripheral blood. We hypothesized that antigen-driven T-cell expansion might best be triggered in vitro by acute activation of innate immunity to mimic a life-threatening infection. Unfractionated peripheral blood mononuclear cells (PBMC) were subjected to a two-step culture, first synchronizing their exposure to exogenous antigens with aggressive surrogate activation of innate immunity, followed by γ-chain cytokine-modulated T-cell hyperexpansion...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/27927165/innate-immunity-based-cancer-immunotherapy-b16-f10-murine-melanoma-model
#18
Veronika Caisová, Andra Vieru, Zuzana Kumžáková, Simona Glaserová, Hana Husníková, Nikol Vácová, Gabriela Krejčová, Lucie Paďouková, Ivana Jochmanová, Katherine I Wolf, Jindřich Chmelař, Jan Kopecký, Jan Ženka
BACKGROUND: Using killed microorganisms or their parts to stimulate immunity for cancer treatment dates back to the end of 19(th) century. Since then, it undergone considerable development. Our novel approach binds ligands to the tumor cell surface, which stimulates tumor phagocytosis. The therapeutic effect is further amplified by simultaneous application of agonists of Toll-like receptors. We searched for ligands that induce both a strong therapeutic effect and are safe for humans. METHODS: B16-F10 murine melanoma model was used...
December 7, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27799314/il-27-is-essential-for-suppression-of-experimental-allergic-asthma-by-the-tlr7-8-agonist-r848-resiquimod
#19
Adan Chari Jirmo, Kathleen Daluege, Christine Happle, Melanie Albrecht, Anna-Maria Dittrich, Mandy Busse, Anika Habener, Jelena Skuljec, Gesine Hansen
Different models of experimental allergic asthma have shown that the TLR7/8 agonist resiquimod (R848) is a potential inhibitor of type 2 helper cell-driven inflammatory responses. However, the mechanisms mediating its therapeutic effects are not fully understood. Using a model of experimental allergic asthma, we show that induction of IL-27 by R848 is critical for the observed ameliorative effects. R848 significantly inhibited all hallmarks of experimental allergic asthma, including airway hyperreactivity, eosinophilic airway inflammation, mucus hypersecretion, and Ag-specific Ig production...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27677654/inhibition-of-cytokine-response-to-tlr-stimulation-and-alleviation-of-collagen-induced-arthritis-in-mice-by-schistosoma-japonicum-peptide-sjmhe1
#20
Xuefeng Wang, Li Li, Jun Wang, Liyang Dong, Yang Shu, Yong Liang, Liang Shi, Chengcheng Xu, Yuepeng Zhou, Yi Wang, Deyu Chen, Chaoming Mao
Helminth-derived products have recently been shown to prevent the development of inflammatory diseases in mouse models. However, most identified immunomodulators from helminthes are mixtures or macromolecules with potentially immunogenic side effects. We previously identified an immunomodulatory peptide called SJMHE1 from the HSP60 protein of Schistosoma japonicum. In this study, we assessed the ability of SJMHE1 to affect murine splenocytes and human peripheral blood mononuclear cells (PBMCs) stimulated by toll-like receptor (TLR) ligands in vitro and its treatment effect on mice with collagen-induced arthritis (CIA)...
March 2017: Journal of Cellular and Molecular Medicine
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