ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Engineering the brain tumor microenvironment enhances the efficacy of dendritic cell vaccination: implications for clinical trial design.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Reprogramming the immune suppressive tumor microenvironment in glioma enhances the efficacy of immune-mediated gene therapy.Molecular therapy. Oncology · 2026Article
- Combined cytotoxic and immune-stimulatory gene therapy using Ad-TK and Ad-Flt3L: Translational developments from rodents to glioma patients.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- The Evolution of Tumor Microenvironment in Gliomas and Its Implication for Target Therapy.International journal of biological sciences · 2023Review
- Review
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- 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
- αB-Crystallin Alleviates Endotoxin-Induced Retinal Inflammation and Inhibits Microglial Activation and Autophagy.Frontiers in immunology · 2021Article
- Single vs. combination immunotherapeutic strategies for glioma.Expert opinion on biological therapy · 2017Review
- Hypoxia promotes glioma-associated macrophage infiltration via periostin and subsequent M2 polarization by upregulating TGF-beta and M-CSFR.Oncotarget · 2016Article
- 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
- Gene Therapy for the Treatment of Neurological Disorders: Central Nervous System Neoplasms.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells.Journal of visualized experiments : JoVE · 2015Article
- Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated macrophages and promotes malignant growth.Nature cell biology · 2015Article
- Overview of current immunotherapeutic strategies for glioma.Immunotherapy · 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
- Consensus guidelines for the detection of immunogenic cell death.Oncoimmunology · 2014Review
- Adenoviral vector-mediated gene therapy for gliomas: coming of age.Expert opinion on biological therapy · 2014Review
- Reciprocal Supportive Interplay between Glioblastoma and Tumor-Associated Macrophages.Cancers · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
purposeGlioblastoma multiforme (GBM) is a deadly primary brain tumor. Clinical trials for GBM using dendritic cell (DC) vaccination resulted in antitumor immune responses. Herein, we tested the hypothesis that combining in situ (intratumoral) Ad-Flt3L/Ad-TK-mediated gene therapy with DC vaccination would increase therapeutic efficacy and antitumor immunity. EXPERIMENTAL
designWe first assessed the immunogenicity of tumor lysates generated by Ad-TK (+GCV), temozolomide (TMZ), or freeze/thawing cycles (FTC) in a syngeneic brain tumor model. We also assessed phenotypic markers, cytokine release, and phagocytosis of bone marrow-derived DCs generated by fms-like tyrosine kinase 3 ligand (Flt3L) + IL-6 or by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL) 4. Inhibition of tumor progression and production of anti-GBM antibodies was assessed following vaccination with (i) tumor cell lysates, (ii) DCs generated with either Flt3L/IL-6 or GM-CSF/IL-4 loaded with either Ad-TK/GCV-, TMZ-, or FTC-generated tumor lysates, or (iii) DCs in combination with in situ Ad-Flt3L/Ad-TK gene therapy.
resultsDCs loaded with tumor cell lysates generated with either Ad-TK/GCV or TMZ led to increased levels of phagocytosis, therapeutic efficacy, and humoral immune response. In situ immunogene therapy in combination with DC vaccination led to brain tumor regression and long-term survival in about 90% of animals, a significant increase when compared with either therapy alone.
conclusionsOur results indicate that modifying the tumor microenvironment using intratumoral Ad-Flt3L/Ad-TK-mediated gene therapy potentiates therapeutic efficacy and antitumor immunity induced by DC vaccination. These data support novel phase I clinical trials to assess the safety and efficacy of this combined approach.
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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.