ArticleJournal of immunotherapy (Hagerstown, Md. : 1997)2012
Evaluation of γ-retroviral vectors that mediate the inducible expression of IL-12 for clinical application.
Article in Journal of immunotherapy (Hagerstown, Md. : 1997), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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, 34 citations in OpenAlex.
- Collagen-binding IL-12-armoured STEAP1 CAR-T cells reduce toxicity and treat prostate cancer in mouse models.Nature biomedical engineering · 2026Article
- Immunotherapy of Hematological Malignancies of Human B-Cell Origin with CD19 CAR T Lymphocytes.Cells · 2024Review
- Safety and feasibility of anti-CD19 CAR T cells expressing inducible IL-7 and CCL19 in patients with relapsed or refractory large B-cell lymphoma.Cell discovery · 2024Article
- Chimeric antigen receptor (CAR) immunotherapy: basic principles, current advances, and future prospects in neuro-oncology.Immunologic research · 2021Review
- Enhanced efficacy and limited systemic cytokine exposure with membrane-anchored interleukin-12 T-cell therapy in murine tumor models.Journal for immunotherapy of cancer · 2020Article
- Optimizing Manufacturing Protocols of Chimeric Antigen Receptor T Cells for Improved Anticancer Immunotherapy.International journal of molecular sciences · 2019Review
- Repurposing endogenous immune pathways to tailor and control chimeric antigen receptor T cell functionality.Nature communications · 2019Article
- Genetic Modification Strategies to Enhance CAR T Cell Persistence for Patients With Solid Tumors.Frontiers in immunology · 2019Review
- Target-Dependent Expression of IL12 by synNotch Receptor-Engineered NK92 Cells Increases the Antitumor Activities of CAR-T Cells.Frontiers in oncology · 2019Article
- Continuous production process of retroviral vector for adoptive T- cell therapy.Biochemical engineering journal · 2018Article
- Augmentation of Antitumor Immunity by Human and Mouse CAR T Cells Secreting IL-18.Cell reports · 2017Article
- Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.Annual review of immunology · 2017Review
- Chimeric Antigen Receptor T cells for B Cell Neoplasms: Choose the Right CAR for You.Current hematologic malignancy reports · 2016Review
- Producer T cells: Using genetically engineered T cells as vehicles to generate and deliver therapeutics to tumors.Oncoimmunology · 2016Review
- CAR models: next-generation CAR modifications for enhanced T-cell function.Molecular therapy oncolytics · 2016Review
- Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance.The Journal of experimental medicine · 2015Article
- Progresses towards safe and efficient gene therapy vectors.Oncotarget · 2015Review
- Tumor-infiltrating lymphocytes genetically engineered with an inducible gene encoding interleukin-12 for the immunotherapy of metastatic melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Regulation of IL-10 and IL-12 production and function in macrophages and dendritic cells.F1000Research · 2015Review
- Exploiting the curative potential of adoptive T-cell therapy for cancer.Immunological reviews · 2014Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The clinical application of interleukin-12 (IL-12) has been hindered by the toxicity associated with its systemic administration. To potentially overcome this problem, we developed a promoter designed to direct IL-12 expression within the tumor environment using an inducible composite promoter containing binding motifs for the nuclear factor of activated T cells (NFAT) linked to a minimal IL-2 promoter. In this study, the NFAT promoter was coupled to a single-chain human IL-12 gene and inserted into 2 γ-retroviral self-inactivating vectors (SERS.NFAT.hIL12 and SERS.NFAT.hIL12.PA2) and 1 γ-retroviral vector (MSGV1.NFAT.hIL.12 PA2). Peripheral blood lymphocytes (PBLs) were double transduced with an antigen-specific T-cell receptor and the 3 NFAT.hIL12 vectors. Evaluation of inducible IL-12 expression, transduction efficiency, and vector production considerations led to the choice of the MSGV1.NFAT.hIL12.PA2 vector for clinical application. MSGV1.NFAT.hIL12.PA2 PG13 retroviral vector producer cell clones were screened by transduction of tumor antigen-specific PBLs. On the basis of expression studies in PBL, clone D3 was chosen to produce clinical-grade viral vector supernatant and was demonstrated to efficiently transduce young tumor-infiltrating lymphocytes (TIL). The vector-transduced young TIL with known tumor recognition demonstrated specific inducible IL-12 production after coculture with HLA-matched tumor targets and had augmented effector function as demonstrated by increased IFN-γ secretion. These results support the clinical application of adoptive transfer of young TIL engineered with the NFAT.hIL12 vector as a new approach for cancer immunotherapy.
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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.