ArticleJournal for immunotherapy of cancer2019
Intratumoral immunotherapy with TLR7/8 agonist MEDI9197 modulates the tumor microenvironment leading to enhanced activity when combined with other immunotherapies.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 3 of them syntheses that pooled it.
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Who cites it
113 citing papers in PubMed, 3 syntheses or guidelines pooled it, 201 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
- Integration of healthy volunteers in early phase clinical trials with immuno-oncological compounds.Frontiers in oncology · 2022Pooled it
- Global research trends on precision cancer medicine-related rashes (2008-2021): A bibliographic study.Frontiers in immunology · 2022Pooled it
- An Open-Label Study of Subcutaneous CpG Oligodeoxynucleotide (PF03512676) in Combination with Trastuzumab in Patients with Metastatic HER2+ Breast Cancer.Cancer control : journal of the Moffitt Cancer CenterTrial
- Innovative immunotherapeutic strategies for thyroid cancer: challenges and opportunities.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- A tumor-on-a-chip model reveals and targets reciprocal macrophage-NK cell crosstalk to advance immunotherapy screening.Microsystems & nanoengineering · 2026Article
- Pygenic acid A, a small-molecule PD-1/SHP-2 inhibitor, enhances efficacy of therapeutic melanoma vaccines and prophylactic influenza vaccines.Virologica Sinica · 2026Article
- Triplet RNA Lipid Nanoparticles for Locoregional Cancer Immunotherapy.Small science · 2026Article
- 3M-052 combined inhibitory anti-TNFR2 synergistically suppresses colon cancer progression.Frontiers in immunology · 2026Article
- In situ DC-primed vaccine combined with CD137 agonist elicits long-lasting antitumor immunity through cDC1-mediated tumor antigen-specific CD8Journal for immunotherapy of cancer · 2025Article
- Review
- Neoadjuvant immunotherapy in squamous cell carcinoma of the head and neck: current evidence and future perspectives.Molecular cancer · 2025Review
- Enhancing Cancer Therapy with TLR7/8 Agonists: Applications in Vaccines and Combination Treatments.Cancers · 2025Review
- Activation of toll‑like receptors by non‑coding RNAs and their fragments (Review).Molecular medicine reports · 2025Review
- Innate Immune Response to Powassan Virus Infection: Progress Toward Infection Control.Vaccines · 2025Review
- Orchestrating intratumoral DC-T cell immunity for enhanced tumor control via radiotherapy-activated TLR7/8 prodrugs in mice.Nature communications · 2025Article
- Tumor-infiltrating myeloid cells; mechanisms, functional significance, and targeting in cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Modulating the tumor microenvironment in a mouse model of colon cancer using a combination of HIF-1α inhibitors and Toll-Like Receptor 7 agonists.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Targeted Delivery of TLR7 Agonists to the Tumor Microenvironment Enhances Tumor Immunity via Activation of Tumor-Resident Myeloid Cells.Bioconjugate chemistry · 2025Article
- Toll-like receptor response to Zika virus infection: progress toward infection control.Npj viruses · 2025Review
53 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 4 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint blockade (ICB) promotes adaptive immunity and tumor regression in some cancer patients. However, in patients with immunologically "cold" tumors, tumor-resident innate immune cell activation may be required to prime an adaptive immune response and so exploit the full potential of ICB. Whilst Toll-like receptor (TLR) agonists have been used topically to successfully treat some superficial skin tumors, systemic TLR agonists have not been well-tolerated.
methodsThe response of human immune cells to TLR7 and 8 agonism was measured in primary human immune cell assays. MEDI9197 (3M-052) was designed as a novel lipophilic TLR7/8 agonist that is retained at the injection site, limiting systemic exposure. Retention of the TLR7/8 agonist at the site of injection was demonstrated using quantitative whole-body autoradiography, HPLC-UV, and MALDI mass spectrometry imaging. Pharmacodynamic changes on T cells from TLR7/8 agonist treated B16-OVA tumors was assessed by histology, quantitative real time PCR, and flow cytometry. Combination activity of TLR7/8 agonism with immunotherapies was assessed in vitro by human DC-T cell MLR assay, and in vivo using multiple syngeneic mouse tumor models.
resultsTargeting both TLR7 and 8 triggers an innate and adaptive immune response in primary human immune cells, exemplified by secretion of IFNα, IL-12 and IFNγ. In contrast, a STING or a TLR9 agonist primarily induces release of IFNα. We demonstrate that the TLR7/8 agonist, MEDI9197, is retained at the sight of injection with limited systemic exposure. This localized TLR7/8 agonism leads to Th1 polarization, enrichment and activation of natural killer (NK) and CD8
conclusionLocalized TLR7/8 agonism can enhance recruitment and activation of immune cells in tumors and polarize anti-tumor immunity towards a Th1 response. Moreover, we demonstrate that the anti-tumor effects of this TLR7/8 agonist can be enhanced through combination with checkpoint inhibitors and co-stimulatory agonists.
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