How immunotherapies are targeting the glioblastoma immune environment

Felthun, Jonathan Zachary; Reddy, Rajesh; McDonald, Kerrie L.

doi:10.1016/j.jocn.2017.10.019

Cited by 8 publications

(4 citation statements)

References 60 publications

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“…The location of the disease and the infiltrative capability of glioblastoma make complete surgical resection extremely difficult. Moreover, chemotherapy and irradiation regimens are not curative; thus, almost all patients experience tumor progression or recurrence that lead to devastating consequences 3 . Since no standard of care is established for recurrent or progressive glioblastoma 4 , the demand for new treatment modalities offering better clinical outcomes for these patients is in high demand.…”

Section: Introductionmentioning

confidence: 99%

GD2 CAR T cells against human glioblastoma

et al. 2021

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Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data highlighted a robust GD2 CAR antitumor potential in 2D and 3D glioblastoma models associated with a significant and CAR T-restricted increase of selected cytokines. Interestingly, immunosuppressant TGF β1, expressed in all co-cultures, did not influence antitumor activity. The orthotopic NOD/SCID models using primary glioblastoma cells reproduced human histopathological features. Considering still-conflicting data on the delivery route for targeting brain tumors, we compared intracerebral versus intravenous CAR T injections. We report that the intracerebral route significantly increased the length of survival time in a dose-dependent manner, without any side effects. Collectively, the proposed anti-GD2 CAR can counteract human glioblastoma potentially opening a new therapeutic option for a still incurable cancer.

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Section: Introductionmentioning

confidence: 99%

GD2 CAR T cells against human glioblastoma

et al. 2021

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“…The United States Food and Drug Administration has approved bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb), to treat recurrent GBM. Despite the progress, the current standard care only provides a median survival of 14.6 months for GBM patients [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Targeted Extracellular Vesicles Delivered Verrucarin A to Treat Glioblastoma

Chen

Guan

et al. 2022

Biomedicines

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Glioblastomas, accounting for approximately 50% of gliomas, comprise the most aggressive, highly heterogeneous, and malignant brain tumors. The objective of this study was to develop and evaluate a new targeted therapy, i.e., highly potent natural compound verrucarin A (Ver-A), delivered with monoclonal antibody-directed extracellular vesicle (mAb-EV). First, the high surface expression of epidermal growth factor receptor (EGFR) in glioblastoma patient tissue and cell lines was confirmed using immunohistochemistry staining, flow cytometry, and Western blotting. mAb-EV-Ver-A was constructed by packing Ver-A and tagging anti-EGFR mAb to EV generated from HEK293F culture. Confocal microscopy and the In Vivo Imaging System demonstrated that mAb-EV could penetrate the blood–brain barrier, target intracranial glioblastoma xenografts, and deliver drug intracellularly. The in vitro cytotoxicity study showed IC50 values of 2–12 nM of Ver-A. The hematoxylin and eosin staining of major organs in the tolerated dose study indicated minimal systemic toxicity of mAb-EV-Ver-A. Finally, the in vivo anti-tumor efficacy study in intracranial xenograft models demonstrated that EGFR mAb-EV-Ver-A effectively inhibited glioblastoma growth, but the combination with VEGF mAb did not improve the therapeutic efficacy. This study suggested that mAb-EV is an effective drug delivery vehicle and natural Ver-A has great potential to treat glioblastoma.

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“…Tumor microenvironment is a concept related to micro cellular signals, receptors, structures, angiogenesis, molecules, etc. In particular, immunosurveillance systems are deeply related to tumor microenvironment, and many articles have recently been published which focus on immunology and microenvironment [13,15,16]. Considering that the word “microenvironment” appeared 146 times in the official abstracts of the Annual Meeting of the Society for Neuro-Oncology (SNO-2017, San Francisco, CA, USA) [17], we can see how this field has recently gained attention of neuro-oncologists.…”

Section: Discussionmentioning

confidence: 99%

Mining-Guided Machine Learning Analyses Revealed the Latest Trends in Neuro-Oncology

Hana

Tanaka

Nejo

et al. 2019

Cancers

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In conducting medical research, a system which can objectively predict the future trends of the given research field is awaited. This study aims to establish a novel and versatile algorithm that predicts the latest trends in neuro-oncology. Seventy-nine neuro-oncological research fields were selected with computational sorting methods such as text-mining analyses. Thirty journals that represent the recent trends in neuro-oncology were also selected. As a novel concept, the annual impact (AI) of each year was calculated for each journal and field (number of articles published in the journal × impact factor of the journal). The AI index (AII) for the year was defined as the sum of the AIs of the 30 journals. The AII trends of the 79 fields from 2008 to 2017 were subjected to machine learning predicting analyses. The accuracy of the predictions was validated using actual past data. With this algorithm, the latest trends in neuro-oncology were predicted. As a result, the linear prediction model achieved relatively good accuracy. The predicted hottest fields in recent neuro-oncology included some interesting emerging fields such as microenvironment and anti-mitosis. This algorithm may be an effective and versatile tool for prediction of future trends in a particular medical field.

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How immunotherapies are targeting the glioblastoma immune environment

Cited by 8 publications

References 60 publications

GD2 CAR T cells against human glioblastoma

GD2 CAR T cells against human glioblastoma

Targeted Extracellular Vesicles Delivered Verrucarin A to Treat Glioblastoma

Mining-Guided Machine Learning Analyses Revealed the Latest Trends in Neuro-Oncology

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