ArticleJournal of immunology (Baltimore, Md. : 1950)2010
IL-12 and IL-27 sequential gene therapy via intramuscular electroporation delivery for eliminating distal aggressive tumors.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. 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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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.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
- Trial
- Intratumoral expression of IL-12 and CD40 ligand (CD154) from plasmids generates antitumor responses that eliminate tumoral T regs.Scientific reports · 2025Article
- Harnessing IL-27: challenges and potential in cancer immunotherapy.Clinical and experimental medicine · 2025Review
- The efficacy and applicability of chimeric antigen receptor (CAR) T cell-based regimens for primary bone tumors: A comprehensive review of current evidence.Journal of bone oncology · 2024Review
- IL-12 and IL-27 Promote CD39 Expression on CD8+ T Cells and Differentially Regulate the CD39+CD8+ T Cell Phenotype.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Intratumoral delivery of IL-12 and IL-27 mRNA using lipid nanoparticles for cancer immunotherapy.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- A Second-Generation Nanoluc-IL27 Fusion Cytokine for Targeted-Gene-Therapy Applications.Bioengineering (Basel, Switzerland) · 2022Article
- Safety levels of systemic IL-12 induced by cDNA expression as a cancer therapeutic.Immunotherapy · 2022Article
- Interleukins and Ischemic Stroke.Frontiers in immunology · 2022Review
- A uracil auxotroph Toxoplasma gondii exerting immunomodulation to inhibit breast cancer growth and metastasis.Parasites & vectors · 2021Article
- Reengineering Tumor Microenvironment with Sequential Interleukin Delivery.Bioengineering (Basel, Switzerland) · 2021Article
- Ligand-Mediated Targeting of Cytokine Interleukin-27 Enhances Its BioactivityMolecular therapy. Methods & clinical development · 2020Article
- Interleukin-27 Gene Delivery Targeting IL-6Rα-Expressing Cells as a Stress Response Therapy.International journal of molecular sciences · 2020Article
- Is AAV-delivered IL-27 a potential immunotherapeutic for cancer?American journal of cancer research · 2020Review
- Review
- IL-27 gene therapy induces depletion of Tregs and enhances the efficacy of cancer immunotherapy.JCI insight · 2018Article
- Tristetraprolin inhibits macrophage IL-27-induced activation of antitumour cytotoxic T cell responses.Nature communications · 2017Article
- Skeletal muscle signal peptide optimization for enhancing propeptide or cytokine secretion.Journal of theoretical biology · 2016Article
- Potential clinical application of interleukin-27 as an antitumor agent.Cancer science · 2015Review
- Epstein-Barr virus-induced gene 3-deficiency leads to impaired antitumor T-cell responses and accelerated tumor growth.Oncoimmunology · 2015Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
Abstract
Eradication of residual malignancies and metastatic tumors via a systemic approach is the key for successfully treating cancer and increasing cancer patient survival. Systemic administration of IL-12 protein in an acute large dose is effective but toxic. Systemic administration of IL-12 gene by persistently expressing a low level of IL-12 protein may reduce the systemic toxicity but only eradicates IL-12-sensitive tumors. In this study, we discovered that sequential administration of IL-12- and IL-27-encoding DNA, referred to as sequential IL-12-->IL-27 (IL-12 administration followed by IL-27 administration 10 d after) gene therapy, not only eradicated IL-12-sensitive CT26 tumors from 100% of mice but also eradicated the highly malignant 4T1 tumors from 33% of treated mice in multiple independent experiments. This IL-12-->IL-27 sequential gene therapy is not only superior to IL-12-encoding plasmid DNA given a total of two times at a 10-d interval sequential gene therapy for eliminating tumors but also for inducing CTL activity, increasing T cell infiltration into tumors, and yielding a large number of tumor-specific IFN-gamma-positive CD8 T cells. Notably, depletion of either T or NK cells during the IL-27 treatment phase reverses tumor eradication, suggesting an NK cell requirement for this sequential gene therapy-mediated tumor eradication. Both reversal of the administration sequence and coadministration of IL-12 and IL-27 impaired tumor eradication in 4T1 tumor-bearing mice. This IL-12-->IL-27 sequential gene therapy, via sequential administration of IL-12- and IL-27-encoding plasmid DNA into tumor-bearing mice through i.m. electroporation, provides a simple but effective approach for eliminating inaccessible residual tumors.
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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.