ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Temozolomide does not impair gene therapy-mediated antitumor immunity in syngeneic brain tumor models.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 36 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
- Development of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy.Current protocols · 2025Article
- Optimization, Characterization, and Comparison of Two Luciferase-Expressing Mouse Glioblastoma Models.Cancers · 2024Article
- The need for paradigm shift: prognostic significance and implications of standard therapy-related systemic immunosuppression in glioblastoma for immunotherapy and oncolytic virotherapy.Frontiers in immunology · 2024Review
- 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
- CD200 Immune-Checkpoint Peptide Elicits an Anti-glioma Response Through the DAP10 Signaling Pathway.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Inhibition of 2-hydroxyglutarate elicits metabolic reprogramming and mutant IDH1 glioma immunity in mice.The Journal of clinical investigation · 2021Article
- Blocking NHE1 stimulates glioma tumor immunity by restoring OXPHOS function of myeloid cells.Theranostics · 2021Article
- Immunocompetent Mouse Models in the Search for Effective Immunotherapy in Glioblastoma.Cancers · 2020Review
- Immune-stimulatory (TK/Flt3L) gene therapy opens the door to a promising new treatment strategy against brainstem gliomas.Oncotarget · 2020Article
- Synthetic High-density Lipoprotein Nanodiscs for Personalized Immunotherapy Against Gliomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Prospects of biological and synthetic pharmacotherapies for glioblastoma.Expert opinion on biological therapy · 2020Review
- Functional characterization of tumor antigen-specific T-cells isolated from the tumor microenvironment of sleeping beauty induced murine glioma models.Methods in enzymology · 2020Article
- Combined-therapeutic strategies synergistically potentiate glioblastoma multiforme treatmentTheranostics · 2020Review
- Drug resistance in glioblastoma: are persisters the key to therapy?Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Modulation of temozolomide dose differentially affects T-cell response to immune checkpoint inhibition.Neuro-oncology · 2019Article
- High-Density Lipoprotein-Mimicking Nanodiscs for Chemo-immunotherapy against Glioblastoma Multiforme.ACS nano · 2019Article
- Current state and future prospects of immunotherapy for glioma.Immunotherapy · 2018Review
- The Role of Immune Checkpoint Inhibition in the Treatment of Brain Tumors.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Review
- The Sequence of Delta24-RGD and TMZ Administration in Malignant Glioma Affects the Role of CD8Molecular therapy oncolytics · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeGlioblastoma multiforme is the most common primary brain cancer in adults. Chemotherapy with temozolomide (TMZ) significantly prolongs the survival of patients with glioblastoma multiforme. However, the three-year survival is still approximately 5%. Herein, we combined intratumoral administration of an adenoviral vector expressing Flt3L (Ad-Flt3L) with systemic temozolomide to assess its impact on therapeutic efficacy. EXPERIMENTAL
designWild-type or immunodeficient mice bearing intracranial glioblastoma multiforme or metastatic melanoma were treated with an intratumoral injection of Ad-Flt3L alone or in combination with the conditionally cytotoxic enzyme thymidine kinase (Ad-TK), followed by systemic administration of ganciclovir and temozolomide. We monitored survival and measured the tumor-infiltrating immune cells.
resultsAlthough treatment with temozolomide alone led to a small improvement in median survival, when used in combination with gene therapy-mediated immunotherapy, it significantly increased the survival of tumor-bearing mice. The antitumor effect was further enhanced by concomitant intratumoral administration of Ad-TK, leading to 50% to 70% long-term survival in all tumor models. Although temozolomide reduced the content of T cells in the tumor, this did not affect the therapeutic efficacy. The antitumor effect of Ad-Flt3L+Ad-TK+TMZ required an intact immune system because the treatment failed when administered to knock out mice that lacked lymphocytes or dendritic cells.
conclusionsOur results challenge the notion that chemotherapy leads to a state of immune-suppression which impairs the ability of the immune system to mount an effective antitumor response. Our work indicates that temozolomide does not inhibit antitumor immunity and supports its clinical implementation in combination with immune-mediated therapies.
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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.