ArticleJournal for immunotherapy of cancer2016
Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma.
Article in Journal for immunotherapy of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 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
45 citing papers in PubMed, 54 citations in OpenAlex.
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- Immunotherapy for glioblastoma: the promise of combination strategies.Journal of experimental & clinical cancer research : CR · 2022Review
- Functional Diversities of Regulatory T Cells in the Context of Cancer Immunotherapy.Frontiers in immunology · 2022Review
- Hijacking Sexual Immuno-Privilege in GBM-An Immuno-Evasion Strategy.International journal of molecular sciences · 2021Article
- Metabolic reprogramming of T regulatory cells in the hypoxic tumor microenvironment.Cancer immunology, immunotherapy : CII · 2021Review
- Immunotherapy in Glioblastoma: A Clinical Perspective.Cancers · 2021Review
- Targeting Treg cells with GITR activation alleviates resistance to immunotherapy in murine glioblastomas.Nature communications · 2021Article
- Challenging Hurdles of Current Targeting in Glioblastoma: A Focus on Immunotherapeutic Strategies.International journal of molecular sciences · 2021Review
- Neuroinflammatory changes of the normal brain tissue in cured mice following combined radiation and anti-PD-1 blockade therapy for glioma.Scientific reports · 2021Article
- Review
- New Immunotherapeutic Approaches for Glioblastoma.Journal of immunology research · 2021Review
- Exploiting Radiation Therapy to Restore Immune Reactivity of Glioblastoma.Frontiers in oncology · 2021Review
- Immunotherapy Resistance in Glioblastoma.Frontiers in genetics · 2021Review
- Optimizing T Cell-Based Therapy for Glioblastoma.Frontiers in immunology · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundGlioblastoma (GBM) is a poorly immunogenic neoplasm treated with focused radiation. Immunotherapy has demonstrated synergistic survival effects with stereotactic radiosurgery (SRS) in murine GBM. GITR is a co-stimulatory molecule expressed constitutively on regulatory T-cells and by effector T-cells upon activation. We tested the hypothesis that anti-GITR monoclonal antibody (mAb) and SRS together would confer an immune-mediated survival benefit in glioma using the orthotopic GL261 glioma model.
methodsMice received SRS and anti-GITR 10 days after implantation. The anti-GITR mAbs tested were formatted as mouse IgG1 D265A (anti-GITR (1)) and IgG2a (anti-GITR (2a)) isotypes. Mice were randomized to four treatment groups: (1) control; (2) SRS; (3) anti-GITR; (4) anti-GITR/SRS. SRS was delivered to the tumor in one fraction, and mice were treated with mAb thrice. Mice were euthanized on day 21 to analyze the immunologic profile of tumor, spleen, and tumor draining lymph nodes.
resultsAnti-GITR (1)/SRS significantly improved survival over either treatment alone (p < .0001) with a cure rate of 24 % versus 0 % in a T-lymphocyte-dependent manner. There was elevated intratumoral CD4+ effector cell infiltration relative to Treg infiltration in mice treated with anti-GITR (1)/SRS, as well as significantly elevated IFNγ and IL-2 production by CD4+ T-cells and elevated IFNγ and TNFα production by CD8+ T-cells. There was increased mRNA expression of M1 markers and decreased expression of M2 markers in tumor infiltrating mononuclear cells. The anti-GITR (2a)/SRS combination did not improve survival, induce tumor regression, or result in Treg depletion.
conclusionsThese findings provide preclinical evidence for the use of anti-GITR (1) non-depleting antibodies in combination with SRS in GBM.
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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.