ArticleProceedings of the National Academy of Sciences of the United States of America2020
Nanoparticle delivery of immunostimulatory oligonucleotides enhances response to checkpoint inhibitor therapeutics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
- Article
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- Glycopolymeric Nanoparticles Block Breast Cancer Growth by Inhibiting Efferocytosis in the Tumor Microenvironment.ACS applied nano materials · 2024Article
- Research Progress of Nanomaterials Acting on NK Cells in Tumor Immunotherapy and Imaging.Biology · 2024Review
- Nanoparticle-Conjugated Toll-Like Receptor 9 Agonists Improve the Potency, Durability, and Breadth of COVID-19 Vaccines.ACS nano · 2024Article
- Chemo-immunotherapy by dual-enzyme responsive peptide self-assembling abolish melanoma.Bioactive materials · 2024Article
- Immunostimulatory DNA Hydrogel Enhances Protective Efficacy of Nanotoxoids against Bacterial Infection.Advanced materials (Deerfield Beach, Fla.) · 2023Article
- Overcoming acquired resistance to cancer immune checkpoint therapy: potential strategies based on molecular mechanisms.Cell & bioscience · 2023Review
- Peptide-Based Nanoparticles for Systemic Extrahepatic Delivery of Therapeutic Nucleotides.International journal of molecular sciences · 2023Review
- Review
- Fn14-Directed DART Nanoparticles Selectively Target Neoplastic Cells in Preclinical Models of Triple-Negative Breast Cancer Brain Metastasis.Molecular pharmaceutics · 2023Article
- How Advanced are Cancer Immuno-Nanotherapeutics? A Comprehensive Review of the Literature.International journal of nanomedicine · 2023Review
- Polymeric microneedles enable simultaneous delivery of cancer immunomodulatory drugs and detection of skin biomarkers.Theranostics · 2023Article
- Photodynamic Stromal Depletion Enhances Therapeutic Nanoparticle Delivery in 3D Pancreatic Ductal Adenocarcinoma Tumor Models.Photochemistry and photobiology · 2023Article
- Toll-like receptor 9 agonists and combination therapies: strategies to modulate the tumour immune microenvironment for systemic anti-tumour immunity.British journal of cancer · 2022Review
- Cancer Resistance to Immunotherapy: Molecular Mechanisms and Tackling Strategies.International journal of molecular sciences · 2022Review
- Molecular ZIP codes in targeted drug delivery.Proceedings of the National Academy of Sciences of the United States of America · 2022Review
- Non-cytotoxic nanoparticles re-educating macrophages achieving both innate and adaptive immune responses for tumor therapy.Asian journal of pharmaceutical sciences · 2022Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The recent advent of immune checkpoint inhibitor (CPI) antibodies has revolutionized many aspects of cancer therapy, but the efficacy of these breakthrough therapeutics remains limited, as many patients fail to respond for reasons that still largely evade understanding. An array of studies in human patients and animal models has demonstrated that local signaling can generate strongly immunosuppressive microenvironments within tumors, and emerging evidence suggests that delivery of immunostimulatory molecules into tumors can have therapeutic effects. Nanoparticle formulations of these cargoes offer a promising way to maximize their delivery and to enhance the efficacy of checkpoint inhibitors. We developed a modular nanoparticle system capable of encapsulating an array of immunostimulatory oligonucleotides that, in some cases, greatly increase their potency to activate inflammatory signaling within immune cells in vitro. We hypothesized that these immunostimulatory nanoparticles could suppress tumor growth by activating similar signaling in vivo, and thereby also improve responsiveness to immune checkpoint inhibitor antibody therapies. We found that our engineered nanoparticles carrying a CpG DNA ligand of TLR9 can suppress tumor growth in several animal models of various cancers, resulting in an abscopal effect on distant tumors, and improving responsiveness to anti-CTLA4 treatment with combinatorial effects after intratumoral administration. Moreover, by incorporating tumor-homing peptides, immunostimulatory nucleotide-bearing nanoparticles facilitate antitumor efficacy after systemic intravenous (i.v.) administration.
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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.