ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2012
Gene therapy-mediated reprogramming tumor infiltrating T cells using IL-2 and inhibiting NF-κB signaling improves the efficacy of immunotherapy in a brain cancer model.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- H3.3-G34R Mutation-Mediated Epigenetic Reprogramming Leads to Enhanced Efficacy of Immune Stimulatory Gene Therapy in Diffuse Hemispheric Gliomas.bioRxiv : the preprint server for biology · 2025Article
- The cholera toxin B subunit induces trained immunity in dendritic cells and promotes CD8 T cell antitumor immunity.Frontiers in immunology · 2024Article
- A biomimetic assay platform for the interrogation of antigen-dependent anti-tumor T-cell function.Communications biology · 2021Article
- Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments.Frontiers in pharmacology · 2021Review
- Current Approaches for Glioma Gene Therapy and Virotherapy.Frontiers in molecular neuroscience · 2021Review
- Immune-stimulatory (TK/Flt3L) gene therapy opens the door to a promising new treatment strategy against brainstem gliomas.Oncotarget · 2020Article
- RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF-κB pathway in oral squamous cell carcinoma.Molecular oncology · 2020Article
- Involvement of local renin-angiotensin system in immunosuppression of tumor microenvironment.Cancer science · 2018Article
- Immunosuppressive Myeloid Cells' Blockade in the Glioma Microenvironment Enhances the Efficacy of Immune-Stimulatory Gene Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia.PloS one · 2017Article
- Preclinical Efficacy and Safety Profile of Allometrically Scaled Doses of Doxycycline Used to Turn "On" Therapeutic Transgene Expression from High-Capacity Adenoviral Vectors in a Glioma Model.Human gene therapy methods · 2016Article
- Induction of antigen-specific cytotoxic T-cell response by dendritic cells generated from ecto-mesenchymal stem cells infected with an adenovirus containing the MAGE-D4a gene.Oncology letters · 2016Article
- A multi-targeted approach to suppress tumor-promoting inflammation.Seminars in cancer biology · 2015Review
- Sustained proliferation in cancer: Mechanisms and novel therapeutic targets.Seminars in cancer biology · 2015Review
- Dendritic Cell-Based Immunotherapy Treatment for Glioblastoma Multiforme.BioMed research international · 2015Review
- Blockade of mTOR signaling via rapamycin combined with immunotherapy augments antiglioma cytotoxic and memory T-cell functions.Molecular cancer therapeutics · 2014Article
- Adenoviral vector-mediated gene therapy for gliomas: coming of age.Expert opinion on biological therapy · 2014Review
- Safety profile, efficacy, and biodistribution of a bicistronic high-capacity adenovirus vector encoding a combined immunostimulation and cytotoxic gene therapy as a prelude to a phase I clinical trial for glioblastoma.Toxicology and applied pharmacology · 2013Article
- Dendritic cell-based immunotherapy for glioma: multiple regimens and implications in clinical trials.Neurologia medico-chirurgica · 2013Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Immune-mediated gene therapy using adenovirus expressing Flt3 ligand and thymidine kinase followed by ganciclovir administration (Flt3/TK) effectively elicits tumor regression in preclinical glioma models. Herein, we assessed new strategies to optimize Flt3L/TK therapeutic efficacy in a refractory RG2 orthotopic glioblastoma model. Specifically, we aimed to optimize the therapeutic efficacy of Flt3L/TK treatment in the RG2 model by overexpressing the following genes within the brain tumor microenvironment: 1) a TK mutant with enhanced cytotoxicity (SR39 mutant TK), 2) Flt3L-IgG fusion protein that has a longer half-life, 3) CD40L to stimulate DC maturation, 4) T helper cell type 1 polarizing dendritic cell cytokines interleukin-12 or C-X-C motif ligand 10 chemokine (CXCL)-10, 5) C-C motif ligand 2 chemokine (CCL2) or C-C motif ligand 3 chemokine (CCL3) to enhance dendritic cell recruitment into the tumor microenvironment, 6) T helper cell type 1 cytokines interferon-γ or interleukin-2 to enhance effector T-cell functions, and 7) IκBα or p65RHD (nuclear factor kappa-B [NF-κB] inhibitors) to suppress the function of Foxp3+ Tregs and enhanced effector T-cell functions. Anti-tumor immunity and tumor specific effector T-cell functions were assessed by cytotoxic T lymphocyte assay and intracellular IFN-γ staining. Our data showed that overexpression of interferon-γ or interleukin-2, or inhibition of the nuclear factor kappa-B within the tumor microenvironment, enhanced cytotoxic T lymphocyte-mediated immune responses and successfully extended the median survival of rats bearing intracranial RG2 when combined with Flt3L/TK. These findings indicate that enhancement of T-cell functions constitutes a critical therapeutic target to overcome immune evasion and enhance therapeutic efficacy for brain cancer. In addition, our study provides novel targets to be used in combination with immune-therapeutic strategies for glioblastoma, which are currently being tested in the clinic.
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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.