ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Immunotherapeutic synergy between anti-CD137 mAb and intratumoral administration of a cytopathic Semliki Forest virus encoding IL-12.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03792724 (Phase I-II Study of Intratumoral Urelumab Combined With Nivolumab in Patients With Solid Tumors), which is not on this map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Phase I-II Study of Intratumoral Urelumab Combined With Nivolumab in Patients With Solid Tumors
Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- CD137 agonists in mice suppress germinal center responses by increasing the immunosuppressive activity of follicular regulatory T-cells.The EMBO journal · 2026Article
- Interleukin-12 Delivery Strategies and Advances in Tumor Immunotherapy.Current issues in molecular biology · 2024Review
- Exploiting innate immunity for cancer immunotherapy.Molecular cancer · 2023Review
- Engineering Non-Human RNA Viruses for Cancer Therapy.Vaccines · 2023Review
- Intratumoral immunotherapy with mRNAs encoding chimeric protein constructs encompassing IL-12, CD137 agonists, and TGF-β antagonists.Molecular therapy. Nucleic acids · 2023Article
- IFNγ is a central node of cancer immune equilibrium.Cell reports · 2023Article
- Alphavirus-Driven Interferon Gamma (IFNg) Expression Inhibits Tumor Growth in Orthotopic 4T1 Breast Cancer Model.Vaccines · 2021Article
- Antitumor efficacy and reduced toxicity using an anti-CD137 Probody therapeutic.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- CD137Cancers · 2021Review
- Review
- CD137, an attractive candidate for the immunotherapy of lung cancer.Cancer science · 2020Review
- Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy.Cells · 2020Review
- Localized Interleukin-12 for Cancer Immunotherapy.Frontiers in immunology · 2020Review
- Short-Term Local Expression of a PD-L1 Blocking Antibody from a Self-Replicating RNA Vector Induces Potent Antitumor Responses.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- An Update on Anti-CD137 Antibodies in Immunotherapies for Cancer.International journal of molecular sciences · 2019Review
- Co-stimulatory and co-inhibitory pathways in cancer immunotherapy.Advances in cancer research · 2019Review
- A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity.Nature communications · 2018Article
- Immunological landscape and immunotherapy of hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2015Review
- Functional expression of CD137 (4-1BB) on T helper follicular cells.Oncoimmunology · 2015Article
- Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014.Journal of translational medicine · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intratumoral injection of Semliki Forest virus encoding interleukin-12 (SFV-IL-12) combines acute expression of IL-12 and stressful apoptosis of infected malignant cells. Agonist antibodies directed to costimulatory receptor CD137 (4-1BB) strongly amplify pre-existing cellular immune responses toward weak tumor antigens. In this study, we provide evidence for powerful synergistic effects of a combined strategy consisting of intratumoral injection of SFV-IL-12 and systemic delivery of agonist anti-CD137 monoclonal antibodies (mAbs), which was substantiated against poorly immunogenic B16 melanomas (B16-OVA and B16.F10) and TC-1 lung carcinomas. Effector CD8(β)(+) T cells were sufficient to mediate complete tumor eradications. Accordingly, there was an intensely synergistic in vivo enhancement of cytotoxic T lymphocytes (CTL)-mediated immunity against the tumor antigens OVA and tyrosine-related protein-2 (TRP-2). This train of phenomena led to long-lasting tumor-specific immunity against rechallenge, attained transient control of the progression of concomitant tumor lesions that were not directly treated with SFV-IL-12 and caused autoimmune vitiligo. Importantly, we found that SFV-IL-12 intratumoral injection induces bright expression of CD137 on most tumor-infiltrating CD8(+) T lymphocytes, thereby providing more abundant targets for the action of the agonist antibody. This efficacious combinatorial immunotherapy strategy offers feasibility for clinical translation since anti-CD137 mAbs are already undergoing clinical trials and development of clinical-grade SFV-IL-12 vectors is in progress.
Indexed as
Identifiers
What OpenQuestion holds
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.