Journal
ONCOIMMUNOLOGY
Volume 11, Issue 1, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2022.2124058
Keywords
Virotherapy; cell-based therapy; immunotherapy; immune checkpoint inhibition (ICI); vaccination; glioma; diffuse midline gliomas (DMG); diffuse intrinsic pontine glioma (DIPG); pediatric neurooncology; pediatric neurosurgery
Categories
Funding
- National Institute of General Medical Sciences [T32GM007753, T32GM144273]
- Mildred Scheel Career Center Frankfurt (Deutsche Krebshilfe)
- Frankfurt Research Funding (FFF) program 'Nachwuchswissenschaftler'
- U.S. Food and Drug Administration [R01FD006368, R01FD005379]
- Cannonball Kids cancer Foundation
- Rally Foundation for Childhood Cancer Research
- CureSearch for Children's Cancer
- V Foundation for Cancer Research
- Hyundai Hope on Wheels
- Andrew McDonough B+ Foundation
- National Pediatric Cancer Foundation
- Pediatric Cancer Research Foundation
- Kaul Pediatric Research Institute
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Diffuse midline gliomas (DMG) are highly aggressive and fatal pediatric brain tumors. Traditional treatments have limited effectiveness, making immunotherapy a promising alternative. This review summarizes various immunotherapy-based treatments for DMG and highlights the clinical success of anti-GD2 CAR-T therapy in patients with diffuse intrinsic pontine glioma (DIPG).
Diffuse midline gliomas (DMG) are a highly aggressive and universally fatal subgroup of pediatric tumors responsible for the majority of childhood brain tumor deaths. Median overall survival is less than 12 months with a 90% mortality rate at 2 years from diagnosis. Research into the underlying tumor biology and numerous clinical trials have done little to change the invariably poor prognosis. Continued development of novel, efficacious therapeutic options for DMGs remains a critically important area of active investigation. Given that DMGs are not amenable to surgical resection, have only limited response to radiation, and are refractory to traditional chemotherapy, immunotherapy has emerged as a promising alternative treatment modality. This review summarizes the various immunotherapy-based treatments for DMG as well as their specific limitations. We explore the use of cell-based therapies, oncolytic virotherapy or immunovirotherapy, immune checkpoint inhibition, and immunomodulatory vaccination strategies, and highlight the recent clinical success of anti-GD2 CAR-T therapy in diffuse intrinsic pontine glioma (DIPG) patients. Finally, we address the challenges faced in translating preclinical and early phase clinical trial data into effective standardized treatment for DMG patients.
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