Activation of innate immune cells through TLR triggers immunomodulating events that enhance cell-mediated immunity, raising the possibility that ligands to these receptors might act as adjuvants in conjunction with T cell activating vaccines. In this report, topical imiquimod, a synthetic TLR7 agonist, significantly enhanced the protective antitumor effects of a live, recombinant listeria vaccine against murine melanoma. This tumor protective effect was not dependent on direct application to the tumor and was associated with an increase in tumor-associated and splenic dendritic cells. Additionally, the combination of imiquimod treatment with prior vaccination led to development of localized vitiligo. These findings indicate that activation of the innate immune system with TLR ligands stimulates dendritic cell activity resulting in a bypass of peripheral tolerance and enhanced antitumor activity. The results of these studies have broad implications for future designs of immunotherapeutic vaccines against tumors and the treatment of metastatic melanoma.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.4049/jimmunol.175.3.1983 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Maternal immune activation by toll-like receptor 7 agonist during mid-gestation increases susceptibility to blood-brain barrier leakage after puberty.
Brain Behav Immun Integr
December 2024
Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
Maternal immune activation (MIA), a maternal stressor, increases risk for neuropsychiatric diseases, such as Major Depressive Disorder in offspring. MIA of toll-like receptor 7 (TLR7) initiates an immune response in mother and fetuses in a sex-selective manner. The paraventricular nucleus of the hypothalamus (PVN), a brain region that is sexually dimorphic and regulates hypothalamic-pituitary-adrenal (HPA) stress responses, have been tied to stress-related behaviors (i.
View Article and Find Full Text PDFPolyphenol-mediated assembly of toll-like receptor 7/8 agonist nanoparticles for effective tumor immunotherapy.
Acta Biomater
December 2024
The Second Affiliated Hospital, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China. Electronic address:
Toll-like receptor (TLR) 7/8 agonists have shown significant potential in tumor immunotherapy. However, the limited pharmacokinetic properties and systemic toxicity resulting from off-target effects limits their biomedical applications. We here report the polyphenol-mediated assembly of resiquimod (R848, a TLR7/8 agonist) nanoparticles (RTP NPs) to achieve tumor-selective immunotherapy while avoiding systemic adverse effects.
View Article and Find Full Text PDFExamination of the potential clinical application of 5DEX-0509R, the tumor macrophage-targeting nanomedicine.
Cytokine
December 2024
Cancer Research Unit, Sumitomo Pharma Co Ltd, Osaka, Japan. Electronic address:
Toll-like receptors (TLRs) are crucial for the detection of infections and activation of downstream signaling pathways that lead to the production of pro-inflammatory cytokines and interferons. Because of their strong immunostimulatory activity, TLRs are thought to be a "double-edged sword" for systemic treatment, even in the cancer field. To solve this, we have developed dextran-based TAM targeting activator conjugate (D-TAC) technology which successfully uses tumor-associated macrophages (TAMs) to deliver the TLR7 agonist DSP-0509.
View Article and Find Full Text PDFAmodiaquine Analogs Are Potent Inhibitors of Interleukin-6 Production Induced by Activation of Toll-Like Receptors Recognizing Pathogen Nucleic Acids.
Biol Pharm Bull
December 2024
Department of Radiation Biosciences, Graduate School of Pharmaceutical Sciences, Tokyo University of Science.
Excessive inflammatory responses to viral infections, known as cytokine storms, are caused by overactivation of endolysosomal Toll-like receptors (TLRs) (TLR3, TLR7, TLR8, and TLR9) and can be lethal, but no specific treatment is available. Some quinoline derivatives with antiviral activity were tried during the recent coronavirus disease 2019 (COVID-19) pandemic, but showed serious toxicity, and their efficacy for treating viral cytokine storms was not established. Here, in order to discover a low-toxicity quinoline derivative as a candidate for controlling virally induced inflammation, we synthesized a series of derivatives of amodiaquine (ADQ), a quinoline approved as an antimalarial, and tested their effects on TLRs-mediated production of inflammatory cytokines and cell viability in vitro.
View Article and Find Full Text PDFPPS-TLR7/8 agonist nanoparticles equip robust anticancer immunity by selectively prolonged activation of dendritic cells.
Biomaterials
May 2025
Wuya college of innovation, Shenyang Pharmaceutical University, No.103, Wenhua Road, Shenyang, 110016, China; Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China. Electronic address:
Checkpoint inhibitor therapies do not benefit all patients, and adjuvants play a critical role in boosting immune responses for effective cancer immunotherapy. However, their systemic toxicity and suboptimal activation kinetics pose significant challenges. Here, this study presented a linker-based strategy to modulate the activation kinetics of Toll-like receptor 7/8 (TLR7/8) agonists delivered via poly (propylene sulfide) nanoparticles (PPS NPs).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!