227 results match your criteria resiquimod r848


Sustained IL-4 priming of macrophages enhances the inflammatory response to TLR7/8 ligand R848.

J Leukoc Biol 2021 May 19. Epub 2021 May 19.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.

Macrophages (Mϕ) are highly plastic, and can acquire a variety of functional phenotypes depending on the presence of different stimuli in their local environment. Mφ stimulated by interleukin (IL)-4 induce an alternative activation state and function as anti-inflammatory cells and promote tissue repair. However, there is overwhelming evidence that IL-4 can play a role in promoting inflammation. Read More

View Article and Full-Text PDF

Polarization of Tumor-Associated Macrophages by Nanoparticle-Loaded Combined with Immunogenic Cell Death for Cancer Immunotherapy.

Nano Lett 2021 May 17;21(10):4231-4240. Epub 2021 May 17.

Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. China.

The tumor immunosuppressive microenvironment greatly limits the efficacy of immunotherapy. Tumor-associated macrophages (TAMs) are the most abundant immunosuppressive cells in the tumor microenvironment, which can inhibit the tumor after converting it to an M1-like phenotype. In addition, immunogenic cell death (ICD) can increase the amount of T lymphocytes in tumors, activating antineoplastic immunity. Read More

View Article and Full-Text PDF

Q493K and Q498H substitutions in Spike promote adaptation of SARS-CoV-2 in mice.

EBioMedicine 2021 May 14;67:103381. Epub 2021 May 14.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China; Key Laboratory of development of veterinary diagnostic products, Ministry of Agriculture, Wuhan, 430070, PR China. Electronic address:

Background: An ideal animal model to study SARS-coronavirus 2 (SARS-CoV-2) pathogenesis and evaluate therapies and vaccines should reproduce SARS-CoV-2 infection and recapitulate lung disease like those seen in humans. The angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, but mice are resistant to the infection because their ACE2 is incompatible with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein .

Methods: SARS-CoV-2 was passaged in BALB/c mice to obtain mouse-adapted virus strain. Read More

View Article and Full-Text PDF

Oxyresveratrol Inhibits R848-Induced Pro-Inflammatory Mediators Release by Human Dendritic Cells Even When Embedded in PLGA Nanoparticles.

Molecules 2021 Apr 7;26(8). Epub 2021 Apr 7.

Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona, Italy.

Oxyresveratrol, a stilbene extracted from the plant Roxb., has been reported to provide a considerable anti-inflammatory activity. Since the mechanisms of this therapeutic action have been poorly clarified, we investigated whether oxyresveratrol affects the release of the pro-inflammatory cytokines IL-12, IL-6, and TNF-α by human dendritic cells (DCs). Read More

View Article and Full-Text PDF

Supramolecular assembly of Toll-like receptor 7/8 agonist into multimeric water-soluble constructs enables superior immune stimulation and .

ACS Appl Bio Mater 2020 May 8;3(5):3187-3195. Epub 2020 Apr 8.

Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, 20850, USA.

Resiquimod or R848 (RSQD) is a Toll-like receptor (TLR) 7/8 agonist which shows promise as vaccine adjuvant due to its potential to promote highly desirable cellular immunity. The development of this small molecule in the field to date has been largely impeded by its rapid clearance and lack of association with vaccine antigens. Here, we report a multimeric TLR 7/8 construct of nano-scale size, which results from a spontaneous self-assembly of RSQD with a water-soluble clinical-stage polymer - poly[di(carboxylatophenoxy)phosphazene] (PCPP). Read More

View Article and Full-Text PDF

Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment.

Int J Nanomedicine 2021 12;16:2775-2787. Epub 2021 Apr 12.

Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Purpose: With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men's health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. Read More

View Article and Full-Text PDF

Hyaluronate-Based Self-Stabilized Nanoparticles for Immunosuppression Reversion and Immunochemotherapy in Osteosarcoma Treatment.

ACS Biomater Sci Eng 2021 04 1;7(4):1515-1525. Epub 2021 Apr 1.

The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.

Immunotherapy is regarded as a potential strategy to combat cancer, especially when immunotherapy is combined with appropriate chemotherapy. However, the immunosuppressive tumor microenvironment (TME) and serious side effects extremely limit the application of immunotherapy. Herein, a self-stabilized hyaluronic acid nanoparticle is synthesized for tumor-targeted delivery of doxorubicin (DOX), cisplatin (CDDP), and resiquimod (R848) in osteosarcoma immunochemotherapy, which is referred to as NP. Read More

View Article and Full-Text PDF

Intratumoral immunotherapy using platelet-cloaked nanoparticles enhances antitumor immunity in solid tumors.

Nat Commun 2021 03 31;12(1):1999. Epub 2021 Mar 31.

Cello Therapeutics, Inc., San Diego, CA, 92121, USA.

Intratumoral immunotherapy is an emerging modality for the treatment of solid tumors. Toll-like receptor (TLR) agonists have shown promise for eliciting immune responses, but systemic administration often results in the development of adverse side effects. Herein, we investigate whether localized delivery of the TLR agonist, resiquimod (R848), via platelet membrane-coated nanoparticles (PNP-R848) elicits antitumor responses. Read More

View Article and Full-Text PDF

Pharmacological Activation of p53 during Human Monocyte to Macrophage Differentiation Attenuates Their Pro-Inflammatory Activation by TLR4, TLR7 and TLR8 Agonists.

Cancers (Basel) 2021 Feb 25;13(5). Epub 2021 Feb 25.

Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.

The transcription factor p53 has well-recognized roles in regulating cell cycle, DNA damage repair, cell death, and metabolism. It is an important tumor suppressor and pharmacological activation of p53 by interrupting its interaction with the ubiquitin E3 ligase mouse double minute 2 homolog (MDM2) is actively explored for anti-tumor therapies. In immune cells, p53 modulates inflammatory responses, but the impact of p53 on macrophages remains incompletely understood. Read More

View Article and Full-Text PDF
February 2021

Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice.

ACS Nano 2021 03 1;15(3):4450-4466. Epub 2021 Mar 1.

Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland.

Nanoparticle-based delivery systems for cancer immunotherapies aim to improve the safety and efficacy of these treatments through local delivery to specialized antigen-presenting cells (APCs). Multifunctional mesoporous silica nanoparticles (MSNs), with their large surface areas, their tunable particle and pore sizes, and their spatially controlled functionalization, represent a safe and versatile carrier system. In this study, we demonstrate the potential of MSNs as a pH-responsive drug carrier system for the anticancer immune-stimulant R848 (resiquimod), a synthetic Toll-like receptor 7 and 8 agonist. Read More

View Article and Full-Text PDF

Niclosamide suppresses the expansion of follicular helper T cells and alleviates disease severity in two murine models of lupus via STAT3.

J Transl Med 2021 02 25;19(1):86. Epub 2021 Feb 25.

The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: Autoantibody production against endogenous cellular components is pathogenic feature of systemic lupus erythematosus (SLE). Follicular helper T (T) cells aid in B cell differentiation into autoantibody-producing plasma cells (PCs). The IL-6 and IL-21 cytokine-mediated STAT3 signaling are crucial for the differentiation to T cells. Read More

View Article and Full-Text PDF
February 2021

peripheral blood mononuclear cell response to R848 in children after supplementation with the probiotic NCFM/ Bi-07.

Benef Microbes 2021 Feb 8;12(1):85-93. Epub 2021 Feb 8.

Department of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53972, USA.

Several studies have demonstrated a decrease in upper respiratory infection (URI) frequency and severity in subjects taking probiotic supplements. We hypothesised beneficial effects of probiotics on viral URI in children are due to modulation of inflammatory innate immune responses. We tested this hypothesis, providing children with a probiotic combination of ssp. Read More

View Article and Full-Text PDF
February 2021

Cyclic Di-Adenosine Monophosphate: A Promising Adjuvant Candidate for the Development of Neonatal Vaccines.

Pharmaceutics 2021 Feb 1;13(2). Epub 2021 Feb 1.

Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.

Underdeveloped immunity during the neonatal age makes this period one of the most dangerous during the human lifespan, with infection-related mortality being one of the highest of all age groups. It is also discussed that vaccination during this time window may result in tolerance rather than in productive immunity, thus raising concerns about the overall vaccine-mediated protective efficacy. Cyclic di-nucleotides (CDN) are bacterial second messengers that are rapidly sensed by the immune system as a danger signal, allowing the utilization of these molecules as potent activators of the immune response. Read More

View Article and Full-Text PDF
February 2021

Integrin αvβ6 cooperates with resiquimod to restore antigen-specific immune tolerance in airway allergy.

Immunol Lett 2021 Feb 29;230:49-58. Epub 2020 Dec 29.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China; Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China. Electronic address:

Background: Integrin αvβ6 can convert the transforming growth factor (TGF)-β precursor to the mature form. Resiquimod (R848) can generate TGF-β-producing regulatory T cells (Treg). Thus, to concurrent administration of specific antigen and R848 may generate antigen-specific Tregs, that is expected to restore immune tolerance in subjects with airway allergic diseases (AAD). Read More

View Article and Full-Text PDF
February 2021

Enhancing antibody-dependent cellular phagocytosis by Re-education of tumor-associated macrophages with resiquimod-encapsulated liposomes.

Biomaterials 2021 01 13;268:120601. Epub 2020 Dec 13.

The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan. Electronic address:

Tumor-associated macrophages (TAMs) exist in nearly all tumors, and form a major part of the tumor microenvironment. TAMs are divided into two groups: tumor-suppressing M1 type and tumor-promoting M2 type. Most TAMs are educated by the tumor cells to become M2 type, which support tumor growth and make immunotherapy ineffective. Read More

View Article and Full-Text PDF
January 2021

Biopolymer Immune Implants' Sequential Activation of Innate and Adaptive Immunity for Colorectal Cancer Postoperative Immunotherapy.

Adv Mater 2021 Jan 9;33(3):e2004559. Epub 2020 Dec 9.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Road, Changchun, 130022, China.

Surgical resection is the first-line therapy for colorectal cancer (CRC). However, for advanced CRC, the curative effect of surgical resection is limited due to either local recurrence or distal metastasis. Postoperative in situ immunotherapy, presents a promising option for preventing tumor recurrence and metastasis, owing to the fact that surgeons have unique opportunities and direct access to the surgical site. Read More

View Article and Full-Text PDF
January 2021

Use of TLR9 and TLR7/8 agonists in combination with d-galactosamine in exploring models for distinct severities of systemic inflammation relative to liver injury.

Authors:
R Seki K Nishizawa

Physiol Res 2020 12 19;69(6):1125-1129. Epub 2020 Nov 19.

Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Tokyo, Japan.

Challenges with various TLR ligands (TLRLs)in combination with D-galactosamine (GalN) in rodents may mimic diverse conditions of acute inflammation and organ failure. Here, we report that CpG (ODN1826, TLR9 agonist)/GalN induced a liver-specific injury with modest systemic effects, whereas R848 (resiquimod, TLR7/8 agonist)/GalN exhibited systemic and liver toxicity. We also observed the protective effect of Gr-1+ cells (the population containing neutrophils) against liver injury in both the R848/GalN and CpG/GalN models. Read More

View Article and Full-Text PDF
December 2020

Injectable Liquid Crystal Formation System for Reshaping Tumor Immunosuppressive Microenvironment to Boost Antitumor Immunity: Postoperative Chemoimmunotherapy.

Small 2020 12 18;16(50):e2004905. Epub 2020 Nov 18.

Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China.

Exploring optimal strategies to improve patient outcome postoperatively is still under challenge. Cancer immunotherapy has great potential to prevent the postoperative tumor recurrence and metastasis, which could be further strengthened by re-education of tumor microenvironment (TME). Herein, a local and sustained drug delivery system of liquid crystal formation system (LCFS) co-loaded with doxorubicin (DOX) and resiquimod (R848) (D/[email protected]) is reported to confer effective chemoimmunotherapy with reduced systematic toxicity. Read More

View Article and Full-Text PDF
December 2020

Development of thermosensitive resiquimod-loaded liposomes for enhanced cancer immunotherapy.

J Control Release 2021 Feb 13;330:1080-1094. Epub 2020 Nov 13.

Molecular Imaging Program, Department of Radiology, Stanford University, 3165 Porter Drive, Palo Alto, CA 94304, USA. Electronic address:

Resiquimod (R848) is a toll-like receptor 7 and 8 (TLR7/8) agonist with potent antitumor and immunostimulatory activity. However, systemic delivery of R848 is poorly tolerated because of its poor solubility in water and systemic immune activation. In order to address these limitations, we developed an intravenously-injectable formulation with R848 using thermosensitive liposomes (TSLs) as a delivery vehicle. Read More

View Article and Full-Text PDF
February 2021

The impact of TLR7 agonist R848 treatment on mast cell phenotype and activity.

Cell Immunol 2021 Jan 28;359:104241. Epub 2020 Oct 28.

Department of Experimental Immunology, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland.

Bearing in mind that mast cell contribution to viral clearance is still not fully understood, in this study, we evaluated the effect of Toll-like receptor (TLR)7 viral single-stranded ribonucleic acid (ssRNA) mimic ligand, namely resiquimod (R)848, on mast cell phenotype and activity. We demonstrated that rat peritoneal mast cells exhibit surface and intracellular expression of ssRNA-specific TLR7 molecule, and that mimic ligand switches the self-expression of this receptor. We also detected other proteins associated with the cellular antiviral response: interferon-alpha receptor 1 (IFNAR1), interferon-gamma receptor 1 (IFNGR1), and major histocompatibility complex I (MHC I). Read More

View Article and Full-Text PDF
January 2021

An Intelligent Biomimetic Nanoplatform for Holistic Treatment of Metastatic Triple-Negative Breast Cancer Photothermal Ablation and Immune Remodeling.

ACS Nano 2020 11 4;14(11):15161-15181. Epub 2020 Nov 4.

The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, P.R. China.

Metastasis is one of the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Immunotherapy brings hope and opportunity to solve this challenge, while its clinical applications are greatly inhibited by the tumor immunosuppressive environment. Here, an intelligent biomimetic nanoplatform was designed based on dendritic large-pore mesoporous silica nanoparticles (DLMSNs) for suppressing metastatic TNBC by combining photothermal ablation and immune remodeling. Read More

View Article and Full-Text PDF
November 2020

Peptide-guided resiquimod-loaded lignin nanoparticles convert tumor-associated macrophages from M2 to M1 phenotype for enhanced chemotherapy.

Acta Biomater 2020 Oct 2. Epub 2020 Oct 2.

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland; Helsinki Institute of Life Science (HiLIFE), University of Helsinki, FI-00014 Helsinki, Finland. Electronic address:

Nanomedicines represent innovative and promising alternative technologies to improve the therapeutic effects of different drugs for cancer ablation. Targeting M2-like tumor-associated macrophages (TAMs) has emerged as a favorable therapeutic approach to fight against cancer through the modulation of the tumor microenvironment. However, the immunomodulatory molecules used for this purpose present side effects upon systemic administration, which limits their clinical translation. Read More

View Article and Full-Text PDF
October 2020

Trial Watch: experimental TLR7/TLR8 agonists for oncological indications.

Oncoimmunology 2020 07 21;9(1):1796002. Epub 2020 Jul 21.

Equipe labellisée par la Ligue Contre le Cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Centre de Recherche des Cordeliers, Paris, France.

Resiquimod (R848) and motolimod (VTX-2337) are second-generation experimental derivatives of imiquimod, an imidazoquinoline with immunostimulatory properties originally approved by the US Food and Drug Administration for the topical treatment of actinic keratosis and genital warts more than 20 years ago. Both resiquimod and motolimod operate as agonists of Toll-like receptor 7 (TLR7) and/or TLR8, in thus far delivering adjuvant-like signals to antigen-presenting cells (APCs). In line with such an activity, these compounds are currently investigated as immunostimulatory agents for the treatment of various malignancies, especially in combination with peptide-based, dendritic cell-based, cancer cell lysate-based, or DNA-based vaccines. Read More

View Article and Full-Text PDF

Activation of Toll-Like Receptors Differentially Modulates Inflammation in the Human Reproductive Tract: Preliminary Findings.

Front Immunol 2020 4;11:1655. Epub 2020 Aug 4.

MISTIC Team, Virology Department, Institut Pasteur, Paris, France.

The female reproductive tract (FRT) is the main site of entry of sexually transmitted infections (STIs). Toll-like receptors (TLRs) that recognize pathogenic motifs are widely expressed in the FRT. TLR stimulation induces immune activation and local production of inflammatory mediators. Read More

View Article and Full-Text PDF

Increased nasal mucosal interferon and CCL13 response to a TLR7/8 agonist in asthma and allergic rhinitis.

J Allergy Clin Immunol 2021 Feb 24;147(2):694-703.e12. Epub 2020 Jul 24.

National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address:

Background: Acute respiratory viral infections are a major cause of respiratory morbidity and mortality, especially in patients with preexisting lung diseases such as asthma. Toll-like receptors are critical in the early detection of viruses and in activating innate immunity in the respiratory mucosa, but there is no reliable and convenient method by which respiratory mucosal innate immune responses can be measured.

Objective: We sought to assess in vivo immune responses to an innate stimulus and compare responsiveness between healthy volunteers and volunteers with allergy. Read More

View Article and Full-Text PDF
February 2021

TJ-M2010-5, a novel MyD88 inhibitor, corrects R848-induced lupus-like immune disorders of B cells in vitro.

Int Immunopharmacol 2020 Aug 5;85:106648. Epub 2020 Jun 5.

Academy of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

B cell hyperactivities are involved in the development of systemic lupus erythematosus (SLE). Toll-like receptor 7 (TLR7) in the B cells plays a pivotal role in the pathogenesis of SLE. Previous studies have focused on the intrinsic role of B cells in TLR7/MyD88 signaling and consequently on immune activation, autoantibody production, and systemic inflammation. Read More

View Article and Full-Text PDF

Human neutrophils activated by TLR8 agonists, with or without IFNγ, synthesize and release EBI3, but not IL-12, IL-27, IL-35, or IL-39.

J Leukoc Biol 2020 11 1;108(5):1515-1526. Epub 2020 Jun 1.

Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.

The IL-12 family of cytokines plays crucial functions in innate and adaptive immunity. These cytokines include heterodimers sharing distinct α (IL-12A, IL-23A, and IL-27A) with two β (IL-12B and Epstein-Barr virus induced gene 3 [EBI3]) chains, respectively, IL-12 (IL-12B plus IL-12A) and IL-23 (IL-12B plus IL-23A) sharing IL-12B, IL-27 (EBI3 plus IL-27A), IL-35 (EBI3 plus IL-12A), and IL-39 (EBI3 plus IL-23A) sharing EBI3. In this context, we have recently reported that highly pure neutrophils incubated with TLR8 agonists produce functional IL-23. Read More

View Article and Full-Text PDF
November 2020

Oral Immunization with HIV-1 Envelope SOSIP trimers elicits systemic immune responses and cross-reactive anti-V1V2 antibodies in non-human primates.

PLoS One 2020 29;15(5):e0233577. Epub 2020 May 29.

Seattle Children's Research Institute, Seattle, WA, United States of America.

Development of a successful HIV vaccine is dependent upon a determination of the optimum antigen and adjuvant as well as choosing an optimal site for vaccine delivery. The site of delivery is particularly relevant as HIV transmission generally requires that the virus crosses a mucosal membrane to infect a new host. Here we undertake a pilot study comparing three vaccine delivery routes, two to the oral cavity (intraepithelial (iEp) and needle-free (NF-Injex)) as well as intramuscular (IM) delivery. Read More

View Article and Full-Text PDF

Photothermally activatable PDA immune nanomedicine combined with PD-L1 checkpoint blockade for antimetastatic cancer photoimmunotherapy.

J Mater Chem B 2019 04 18;7(15):2499-2511. Epub 2019 Mar 18.

Tianjin Key Laboratory of Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.

Photothermal therapy (PTT) has shown promising potential and bright prospects in damaging primary tumors; however, it is limited to metastatic and recrudescent tumors as PTT requires straightforward light irradiation. Moreover, metastatic and recrudescent tumor immunosuppression due to host T-cell antitumor activity is dramatically impeded because of programmed cell death 1 ligand (PD-L1) and programmed cell death receptor 1 (PD-1) pathways and immune checkpoint blockade (ICB) therapy. In this work, we demonstrate that PTT combined with ICB could not only eliminate primary tumors, but also prevent tumor metastasis to the lungs/liver. Read More

View Article and Full-Text PDF

The effect of polyclonal activators on rabbit B cell antibody production.

Res Vet Sci 2020 Jun 14;130:193-196. Epub 2020 Mar 14.

Veterinary Research Institute, Brno, Czech Republic. Electronic address:

Stimulation with polyclonal activators is a tool to increase antibody secretion in B cells. The aim of the present study was to select the most effective common commercially available polyclonal activators of rabbit B cells. Specifically, type B oligodeoxynucleotides with unmethylated deoxycytidyl-deoxyguanosine dinucleotides (CpG-ODN), recombinant rabbit interleukin-2 (rrIL-2), lipopolysaccharide (LPS), pokeweed mitogen (PWM) and Resiquimod (R848) were tested on B cells isolated from blood and spleen by fluorescence-activated cell sorting. Read More

View Article and Full-Text PDF