Engineered cells as glioblastoma therapeutics

Ramanathan, Aparna; Lorimer, Ian A. J.

doi:10.1038/s41417-021-00320-w

Cited by 9 publications

(6 citation statements)

References 93 publications

(98 reference statements)

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“…Glioblastoma multiforme (GBM) is one of the most aggressive types of cancer that initiates in the brain. Despite advancements in our understanding of GBM pathogenesis, the development of new diagnostic tools and innovative targeted therapeutics, GBM remains an incurable disease with a median overall survival (OS) approximately ranging from 7 to 15 months [ 1 , 2 ]. The lack of an effective treatment has been linked to different factors, including target selection, tumour heterogeneity, immunosuppressive tumour microenvironment (TME) and poor penetration of therapeutic agents through the blood–brain barrier (BBB) [ 2 , 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular LGALS3BP: a potential disease marker and actionable target for antibody–drug conjugate therapy in glioblastoma

et al. 2023

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Glioblastoma multiforme (GBM) is a lethal disease characterized by an overall survival of about 1 year, making it one of the most aggressive tumours, with very limited therapeutic possibilities. Specific biomarkers for early diagnosis as well as innovative therapeutic strategies are urgently needed to improve the management of this deadly disease. In this work, we demonstrated that vesicular galectin‐3‐binding protein (LGALS3BP), a glycosylated protein overexpressed in a variety of human malignancies, is a potential GBM disease marker and can be efficiently targeted by a specific antibody–drug conjugate (ADC). Immunohistochemical analysis on patient tissues showed that LGALS3BP is highly expressed in GBM and, compared with healthy donors, the amount of vesicular but not total circulating protein is increased. Moreover, analysis of plasma‐derived extracellular vesicles from mice harbouring human GBM revealed that LGALS3BP can be used for liquid biopsy as a marker of disease. Finally, an ADC targeting LGALS3BP, named 1959‐sss/DM4, specifically accumulates in tumour tissue, producing a potent and dose‐dependent antitumor activity. In conclusion, our work provides evidence that vesicular LGALS3BP is a potential novel GBM diagnostic biomarker and therapeutic target deserving further preclinical and clinical validation.

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Section: Introductionmentioning

confidence: 99%

Extracellular LGALS3BP: a potential disease marker and actionable target for antibody–drug conjugate therapy in glioblastoma

et al. 2023

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“…GBM is the most invasive primary brain tumor with poor clinical outcomes. The poor outcome for GBM patients is partly due to the lack of new therapeutic approaches (Ramanathan & Lorimer, 2021; Tamimi & Juweid, 2017). HSV‐TK/GCV gene therapy is one of the hopeful options for GBM treatment (Li et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine enhances the antitumor effect of olfactory ensheathing cell‐thymidine kinase/ganciclovir gene therapy in human glioblastoma multiforme cells through upregulation of Connexin43 levels

Hosseindoost,

Dehpour,

Dehghan

et al. 2023

Drug Development Research

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Glioblastoma multiforme (GBM) is the most invasive form of primary brain astrocytoma, resulting in poor clinical outcomes. Herpes simplex virus thymidine kinase/ganciclovir (HSV‐TK/GCV) gene therapy is considered a promising strategy for GBM treatment. Since Connexin43 (Cx43) expression is reduced in GBM cells, increasing Cx43 levels could enhance the effectiveness of gene therapy. The present study aims to examine the impact of fluoxetine on HSV‐TK/GCV gene therapy in human GBM cells using human olfactory ensheathing cells (OECs) as vectors. The effect of fluoxetine on Cx43 levels was assessed using the western blot technique. GBM‐derived astrocytes and OECs‐TK were Cocultured, and the effect of fluoxetine on the Antitumor effect of OEC‐TK/GCV gene therapy was evaluated using MTT assay and flow cytometry. Our results showed that fluoxetine increased Cx43 levels in OECs and GBM cells and augmented the killing effect of OECs‐TK on GBM cells. Western blot data revealed that fluoxetine enhanced the Bax/Bcl2 ratio and the levels of cleaved caspase‐3 in the coculture of OECs‐TK and GBM cells. Moreover, flow cytometry data indicated that fluoxetine increased the percentage of apoptotic cells in the coculture system. This study suggests that fluoxetine, by upregulating Cx43 levels, could strengthen the Antitumor effect of OEC‐TK/GCV gene therapy on GBM cells.

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“…Several studies have already established the importance of NK cells in cancer research by highlighting how NK cell deficiency leads to a greater risk of developing cancer [ 102 , 103 , 104 , 105 ]. Incidentally, these cells have not been as well explored as T cells for treating glioblastoma [ 106 ]. Interestingly, in GBM patients, NK cells have shown to behave differently compared with healthy patients by expressing low levels of the NKG2D receptor that usually activates the NK cells to carry out cell-mediated killing of the tumor cells [ 82 , 107 ].…”

Section: Glioma Immune Landscapementioning

confidence: 99%

The Glioma Immune Landscape: A Double-Edged Sword for Treatment Regimens

Mahajan

Schmidt

Schumann

2023

Cancers

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Immune cells constitute a major part of the tumor microenvironment, thereby playing an important role in regulating tumor development. They interact with tumor cells, resulting in the suppression or promotion of glioma development. Therefore, in recent years, scientists have focused on immunotherapy that involves enhancing the immune response to fight the battle against cancer more effectively. While it has shown success against different cancer types, immunotherapy faces major roadblocks in glioma treatment. These involve the blood brain barrier, tumor heterogeneity and an immunosuppressive glioma microenvironment, among other factors. Additionally, the interaction of the peripheral immune system with the central nervous system provides another challenge for immunotherapeutic regimens. For modulating different immune cell populations to counter glioma cells, it is important to expand our knowledge about their role within the glioma microenvironment; therefore, herein, we review the different immune cell populations found in the glioma microenvironment and navigate through the various shortcomings of current immunotherapies for glioma. We conclude by providing an insight into ongoing pre-clinical and clinical trials for glioma therapies.

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Engineered cells as glioblastoma therapeutics

Cited by 9 publications

References 93 publications

Extracellular LGALS3BP: a potential disease marker and actionable target for antibody–drug conjugate therapy in glioblastoma

Extracellular LGALS3BP: a potential disease marker and actionable target for antibody–drug conjugate therapy in glioblastoma

Fluoxetine enhances the antitumor effect of olfactory ensheathing cell‐thymidine kinase/ganciclovir gene therapy in human glioblastoma multiforme cells through upregulation of Connexin43 levels

The Glioma Immune Landscape: A Double-Edged Sword for Treatment Regimens

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