ArticlePloS one2012
An IL12-IL2-antibody fusion protein targeting Hodgkin's lymphoma cells potentiates activation of NK and T cells for an anti-tumor attack.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 43 citations in OpenAlex.
- Click-to-Release for Controlled Immune Cell Activation: Tumor-Targeted Unmasking of an IL12 Prodrug.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Trifunctional antibody-cytokine fusion protein formats for tumor-targeted combination of IL-15 with IL-7 or IL-21.Frontiers in immunology · 2025Article
- Novel OX40 and 4-1BB derived spacers enhance CD30 CAR activity and safety in CD30 positive lymphoma models.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- CLN-617 Retains IL2 and IL12 in Injected Tumors to Drive Robust and Systemic Immune-Mediated Antitumor Activity.Cancer immunology research · 2024Article
- Tumor-Homing Antibody-Cytokine Fusions for Cancer Therapy.OncoTargets and therapy · 2024Review
- Strategies to therapeutically modulate cytokine action.Nature reviews. Drug discovery · 2023Review
- An Antibody Targeting Fibroblast Activation Protein Simultaneously Fused to Interleukin-2 and Tumor Necrosis Factor Selectively Localizes to Neoplastic Lesions.Antibodies (Basel, Switzerland) · 2023Article
- Administration of fusion cytokines induces tumor regression and systemic antitumor immunity.MedComm · 2021Article
- Humanized CD30-Targeted Chimeric Antigen Receptor T Cells Exhibit Potent Preclinical Activity Against Hodgkin's Lymphoma Cells.Frontiers in cell and developmental biology · 2021Article
- Localized Interleukin-12 for Cancer Immunotherapy.Frontiers in immunology · 2020Review
- Evolving Antibody Therapies for the Treatment of Type 1 Diabetes.Frontiers in immunology · 2020Review
- Antibody-cytokine fusion proteins: A novel class of biopharmaceuticals for the therapy of cancer and of chronic inflammation.New biotechnology · 2019Review
- Anti-cancer Therapies Employing IL-2 Cytokine Tumor Targeting: Contribution of Innate, Adaptive and Immunosuppressive Cells in the Anti-tumor Efficacy.Frontiers in immunology · 2018Review
- Drug discovery and therapeutic delivery for the treatment of B and T cell tumors.Advanced drug delivery reviews · 2017Review
- Production of an active anti-CD20-hIL-2 immunocytokine in Nicotiana benthamiana.Plant biotechnology journal · 2016Article
- New insights into IL-12-mediated tumor suppression.Cell death and differentiation · 2015Review
- Emerging role of Natural killer cells in oncolytic virotherapy.ImmunoTargets and therapy · 2015Review
- Activation of CD1d-restricted natural killer T cells can inhibit cancer cell proliferation during chemotherapy by promoting the immune responses in murine mesothelioma.Cancer immunology, immunotherapy : CII · 2014Article
- The natural product phyllanthusmin C enhances IFN-γ production by human NK cells through upregulation of TLR-mediated NF-κB signaling.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Advantages and clinical applications of natural killer cells in cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2014Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Successful immunotherapy of Hodgkin's disease is so far hampered by the striking unresponsiveness of lymphoma infiltrating immune cells. To mobilize both adoptive and innate immune cells for an anti-tumor attack we fused the pro-inflammatory cytokines IL2 and IL12 to an anti-CD30 scFv antibody in a dual cytokine fusion protein to accumulate both cytokines at the malignant CD30(+) Hodgkin/Reed-Sternberg cells in the lymphoma lesion. The tumor-targeted IL12-IL2 fusion protein was superior in activating resting T cells to amplify and secrete pro-inflammatory cytokines compared to targeted IL2 or IL12 alone. NK cells were also activated by the dual cytokine protein to secrete IFN-γ and to lyse target cells. The tumor-targeted IL12-IL2, when applied by i.v. injection to immune-competent mice with established antigen-positive tumors, accumulated at the tumor site and induced tumor regression. Data demonstrate that simultaneous targeting of two cytokines in a spatial and temporal simultaneous fashion to pre-defined tissues is feasible by a dual-cytokine antibody fusion protein. In the case of IL12 and IL2, this produced superior anti-tumor efficacy implying the strategy to muster a broader immune cell response in the combat against cancer.
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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.