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GLIOMA-05 A NOVEL CONCEPT FOR TREATMENT OF GLIOBLASTOMA: VAGUS NERVE ELECTRICAL STIMULATION FOR SUPPRESSION OF CYTOKINE (IL-6) SIGNALING

Glioblastoma is an aggressive, incurable cancer. Innovative approaches are urgently needed. There is resurgent interest in harnessing the power of the immune system (O’Rourke DM, 2017; Liau LM, 2023). Glioblastoma is a key target for cytokine reprogramming of the tumor microenvironment involving mac...

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Autor principal: Brem, Steven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616581/
http://dx.doi.org/10.1093/noajnl/vdad121.004
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author Brem, Steven
author_facet Brem, Steven
author_sort Brem, Steven
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description Glioblastoma is an aggressive, incurable cancer. Innovative approaches are urgently needed. There is resurgent interest in harnessing the power of the immune system (O’Rourke DM, 2017; Liau LM, 2023). Glioblastoma is a key target for cytokine reprogramming of the tumor microenvironment involving macrophages, monocytes, lymphocytes, and myeloid-derived cells. Furthermore, as with other cancers, the incidence and poor prognosis is linked to the age of the patient, and chronic, low-grade inflammation, or “inflammaging” (Franceschi, 2014). There is strong clinical, genomic (Coppola, 2014), preclinical data linking the progression of glioblastoma to the cytokine, IL-6. Yi Fan and colleagues (Wang, 2018; Yang, 2021) showed that blockade of IL-6 increases survival in mouse models of glioblastoma, an effect enhanced with the use of immune checkpoint blockade (ICB). These results were validated and extended by others (Tsukamoto, 2018; Lamano,2019). Taken together, we translated the findings to a prospective, multicenter clinical trial (NRG BRAIN-010, NCT04729959; PI, Stephen Bagley) for recurrent glioblastoma, combining stereotactic radiosurgery, IL-6R blockade (tocilizumab) and ICB (atezolizumab). To date, the regimen is well-tolerated with an acceptable safety profile. Vagus nerve stimulation is FDA-approved for control of medically refractory epilepsy. It is currently being evaluated in a multicenter, pivotal trial to treat advanced rheumatoid arthritis (RESET-RA, NCT04539964). Electrical stimulation of the vagus nerve activates the inflammatory reflex (Kelly, 2022), with a reduction of inflammatory cytokines, including IL-6 (Koopman, 2016). Electrical stimulation of the vagus nerve uses the ‘inflammatory reflex’ and exploits the cholinergic effect on T-cells (Levine, 2020). Taken together, we now propose a clinical trial to assess the safety and efficacy of vagal nerve stimulation for patients with glioblastoma and are in discussion with industry (SetPoint Medical) to design a prospective, clinical trial for treatment of glioblastoma.
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spelling pubmed-106165812023-11-01 GLIOMA-05 A NOVEL CONCEPT FOR TREATMENT OF GLIOBLASTOMA: VAGUS NERVE ELECTRICAL STIMULATION FOR SUPPRESSION OF CYTOKINE (IL-6) SIGNALING Brem, Steven Neurooncol Adv Final Category: Glioma Glioblastoma is an aggressive, incurable cancer. Innovative approaches are urgently needed. There is resurgent interest in harnessing the power of the immune system (O’Rourke DM, 2017; Liau LM, 2023). Glioblastoma is a key target for cytokine reprogramming of the tumor microenvironment involving macrophages, monocytes, lymphocytes, and myeloid-derived cells. Furthermore, as with other cancers, the incidence and poor prognosis is linked to the age of the patient, and chronic, low-grade inflammation, or “inflammaging” (Franceschi, 2014). There is strong clinical, genomic (Coppola, 2014), preclinical data linking the progression of glioblastoma to the cytokine, IL-6. Yi Fan and colleagues (Wang, 2018; Yang, 2021) showed that blockade of IL-6 increases survival in mouse models of glioblastoma, an effect enhanced with the use of immune checkpoint blockade (ICB). These results were validated and extended by others (Tsukamoto, 2018; Lamano,2019). Taken together, we translated the findings to a prospective, multicenter clinical trial (NRG BRAIN-010, NCT04729959; PI, Stephen Bagley) for recurrent glioblastoma, combining stereotactic radiosurgery, IL-6R blockade (tocilizumab) and ICB (atezolizumab). To date, the regimen is well-tolerated with an acceptable safety profile. Vagus nerve stimulation is FDA-approved for control of medically refractory epilepsy. It is currently being evaluated in a multicenter, pivotal trial to treat advanced rheumatoid arthritis (RESET-RA, NCT04539964). Electrical stimulation of the vagus nerve activates the inflammatory reflex (Kelly, 2022), with a reduction of inflammatory cytokines, including IL-6 (Koopman, 2016). Electrical stimulation of the vagus nerve uses the ‘inflammatory reflex’ and exploits the cholinergic effect on T-cells (Levine, 2020). Taken together, we now propose a clinical trial to assess the safety and efficacy of vagal nerve stimulation for patients with glioblastoma and are in discussion with industry (SetPoint Medical) to design a prospective, clinical trial for treatment of glioblastoma. Oxford University Press 2023-10-31 /pmc/articles/PMC10616581/ http://dx.doi.org/10.1093/noajnl/vdad121.004 Text en © The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Final Category: Glioma
Brem, Steven
GLIOMA-05 A NOVEL CONCEPT FOR TREATMENT OF GLIOBLASTOMA: VAGUS NERVE ELECTRICAL STIMULATION FOR SUPPRESSION OF CYTOKINE (IL-6) SIGNALING
title GLIOMA-05 A NOVEL CONCEPT FOR TREATMENT OF GLIOBLASTOMA: VAGUS NERVE ELECTRICAL STIMULATION FOR SUPPRESSION OF CYTOKINE (IL-6) SIGNALING
title_full GLIOMA-05 A NOVEL CONCEPT FOR TREATMENT OF GLIOBLASTOMA: VAGUS NERVE ELECTRICAL STIMULATION FOR SUPPRESSION OF CYTOKINE (IL-6) SIGNALING
title_fullStr GLIOMA-05 A NOVEL CONCEPT FOR TREATMENT OF GLIOBLASTOMA: VAGUS NERVE ELECTRICAL STIMULATION FOR SUPPRESSION OF CYTOKINE (IL-6) SIGNALING
title_full_unstemmed GLIOMA-05 A NOVEL CONCEPT FOR TREATMENT OF GLIOBLASTOMA: VAGUS NERVE ELECTRICAL STIMULATION FOR SUPPRESSION OF CYTOKINE (IL-6) SIGNALING
title_short GLIOMA-05 A NOVEL CONCEPT FOR TREATMENT OF GLIOBLASTOMA: VAGUS NERVE ELECTRICAL STIMULATION FOR SUPPRESSION OF CYTOKINE (IL-6) SIGNALING
title_sort glioma-05 a novel concept for treatment of glioblastoma: vagus nerve electrical stimulation for suppression of cytokine (il-6) signaling
topic Final Category: Glioma
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616581/
http://dx.doi.org/10.1093/noajnl/vdad121.004
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