ArticleJournal for immunotherapy of cancer2021
Intratumoral co-injection of the poly I:C-derivative BO-112 and a STING agonist synergize to achieve local and distant anti-tumor efficacy.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The trial behind it
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- CT-guided intratumoral immunotherapy for advanced solid tumors: a prospective clinical study of safety and systemic antitumor effects.Frontiers in immunology · 2026Trial
- Neoadjuvant BO-112 and Hypofractionated Radiation Therapy with or without Nivolumab in Soft-Tissue Sarcoma: Preclinical and Phase I Results.Cancer discovery · 2026Article
- DNA delivered by lipid nanoparticles induces CD8+ T cell-dependent antitumor responses and enhances anti-PD-L1 therapy.JCI insight · 2026Article
- Triplet RNA Lipid Nanoparticles for Locoregional Cancer Immunotherapy.Small science · 2026Article
- Recent advances in tumor-activated prodrug nanoparticles for cancer immunotherapy.Frontiers in immunology · 2026Review
- Development of nanoparticle-based Toll-like receptor agonists for respiratory immunotherapy.EXCLI journal · 2026Review
- Targeting pattern recognition receptors for cancer therapy: Mechanisms and strategies.Acta pharmaceutica Sinica. B · 2025Review
- Cross-priming in cancer immunology and immunotherapy.Nature reviews. Cancer · 2025Review
- Endoplasmic Reticulum-Targeted Phototherapy Remodels the Tumor Immunopeptidome to Enhance Immunogenic Cell Death and Adaptive Anti-Tumor Immunity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies.iScience · 2024Article
- Therapeutic Immunomodulation of Tumor-Lymphatic Crosstalk via Intratumoral Immunotherapy.Molecular pharmaceutics · 2024Review
- Efficacy of LCMV-based cancer immunotherapies is unleashed by intratumoral injections of polyI:C.Journal for immunotherapy of cancer · 2024Article
- Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies.bioRxiv : the preprint server for biology · 2024Article
- Local therapy with combination TLR agonists stimulates systemic anti-tumor immunity and sensitizes tumors to immune checkpoint blockade.Oncoimmunology · 2024Article
- Cytoplasmic-delivery of polyinosine-polycytidylic acid inhibits pancreatic cancer progression increasing survival by activating Stat1-CCL2-mediated immunity.Journal for immunotherapy of cancer · 2023Article
- Systemic infusion of TLR3-ligand and IFN-α in patients with breast cancer reprograms local tumor microenvironments for selective CTL influx.Journal for immunotherapy of cancer · 2023Article
- Intratumoral immunotherapy with mRNAs encoding chimeric protein constructs encompassing IL-12, CD137 agonists, and TGF-β antagonists.Molecular therapy. Nucleic acids · 2023Article
- Intratumoral Immunotherapy: Is It Ready for Prime Time?Current oncology reports · 2023Review
- Synergistic effects of combined immunotherapy strategies in a model of multifocal hepatocellular carcinoma.Cell reports. Medicine · 2023Article
- Combination of photodynamic therapy and stimulator of interferon genes (STING) agonist inhibits colorectal tumor growth and recurrence.Cancer communications (London, England) · 2023Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBO-112 is a nanoplexed form of polyinosinic:polycytidylic acid that acting on toll-like receptor 3 (TLR3), melanoma differentiation-associated protein 5 (MDA5) and protein kinase RNA-activated (PKR) elicits rejection of directly injected transplanted tumors, but has only modest efficacy against distant untreated tumors. Its clinical activity has also been documented in early phase clinical trials. The 5,6-dimethylxanthenone-4-acetic acid (DMXAA) stimulator of interferon genes (STING) agonist shows a comparable pattern of efficacy when used via intratumoral injections.
methodsMice subcutaneously engrafted with bilateral MC38 and B16.OVA-derived tumors were treated with proinflammatory immunotherapy agents known to be active when intratumorally delivered. The combination of BO-112 and DMXAA was chosen given its excellent efficacy and the requirements for antitumor effects were studied on selective depletion of immune cell types and in gene-modified mouse strains lacking basic leucine zipper ATF-like transcription factor 3 (BATF3), interferon-α/β receptor (IFNAR) or STING. Spatial requirements for the injections were studied in mice bearing three tumor lesions.
resultsBO-112 and DMXAA when co-injected in one of the lesions of mice bearing concomitant bilateral tumors frequently achieved complete local and distant antitumor efficacy. Synergistic effects were contingent on CD8 T cell lymphocytes and dependent on conventional type 1 dendritic cells, responsiveness to type I interferon (IFN) and STING function in the tumor-bearing host. Efficacy was preserved even if BO-112 and DMXAA were injected in separate lesions in a manner able to control another untreated third-party tumor. Efficacy could be further enhanced on concurrent PD-1 blockade.
conclusionClinically feasible co-injections of BO-112 and a STING agonist attain synergistic efficacy able to eradicate distant untreated tumor lesions.
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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.