ArticleScience advances2023
Engineering kinetics of TLR7/8 agonist release from bottlebrush prodrugs enables tumor-focused immune stimulation.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- Generalizable Strategies for the Synthesis of Cereblon-Recruiting PROTAC Prodrugs.Angewandte Chemie (International ed. in English) · 2026Article
- Engineering nanoparticle surface chemistry for antigen-presenting cell targeting improves specificity and safety of TLR3 agonist cancer immunotherapy.bioRxiv : the preprint server for biology · 2026Article
- Antibody-bottlebrush prodrug conjugates for targeted cancer therapy.Nature biotechnology · 2026Article
- Myeloid compartment reprogramming through nanoparticle-delivered resiquimod blocks paracrine growth support and activates phagocytosis to slow tumor progression in endogenous mouse medulloblastoma and diffuse midline glioma models.bioRxiv : the preprint server for biology · 2026Article
- Precise delivery and controlled release: strategies and advances in TLR7/8 agonist prodrugs for cancer immunotherapy.Frontiers in immunology · 2026Review
- X-ray-driven nanomotor with enhanced penetration and retention for carbon monoxide-amplified radioimmunotherapy of advanced colorectal cancer.Materials today. Bio · 2025Article
- Polypept(o)ide Based Biodegradable Cylindrical Polymer Brushes: Controlling Size, Shape, Surface Functionality, and Stability.ACS applied materials & interfaces · 2025Article
- Self-propelled gas nanomotor-integrated microneedles for melanoma therapy: Dual-action in situ eradication and metastatic suppression.Materials today. Bio · 2025Article
- Potentiating cancer immunotherapies with modular albumin-hitchhiking nanobody-STING agonist conjugates.Nature biomedical engineering · 2025Article
- Advances and Strategies in Enhancing mRNA Cancer Vaccines.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Polypept(o)ide-Based Core-Shell Bottlebrush Polymers: A Versatile Platform for Drug Encapsulation.Macromolecular bioscience · 2025Article
- Single atom engineering for radiotherapy-activated immune agonist prodrugs.Nature communications · 2025Article
- CpG-Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2-Mediated Remodeling of Tumor-Associated Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Comparison of Polypentenamer and Polynorbornene Bottlebrushes in Dilute Solution.ACS polymers Au · 2024Article
- Caspase-3-Responsive, Fluorogenic Bivalent Bottlebrush Polymers.ACS macro letters · 2024Article
- Glycan-costumed virus-like particles promote type 1 anti-tumor immunity.bioRxiv : the preprint server for biology · 2024Article
- Design and Evaluation of Synthetic Delivery Formulations for Peptide-Based Cancer Vaccines.BME frontiers · 2024Article
- Thiol-triggered deconstruction of bifunctional silyl ether terpolymersChemical science · 2023Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Imidazoquinolines (IMDs), such as resiquimod (R848), are of great interest as potential cancer immunotherapies because of their ability to activate Toll-like receptor 7 (TLR7) and/or TLR8 on innate immune cells. Nevertheless, intravenous administration of IMDs causes severe immune-related toxicities, and attempts to improve their tissue-selective exposure while minimizing acute systemic inflammation have proven difficult. Here, using a library of R848 "bottlebrush prodrugs" (BPDs) that differ only by their R848 release kinetics, we explore how the timing of R848 exposure affects immune stimulation in vitro and in vivo. These studies led to the discovery of R848-BPDs that exhibit optimal activation kinetics to achieve potent stimulation of myeloid cells in tumors and substantial reductions in tumor growth following systemic administration in mouse syngeneic tumor models without any observable systemic toxicity. These results suggest that release kinetics can be tuned at the molecular level to provide safe yet effective systemically administered immunostimulant prodrugs for next-generation cancer immunotherapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.