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Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
Immunotherapy approaches for the treatment of diffuse midline gliomas
Joshua D Bernstock1,2,3, Samantha E Hoffman4, Ari D Kappel1,2
1Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Abstract:
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.
Insights
Diffuse midline gliomas (DMG) are aggressive pediatric brain tumors with poor prognosis. Immunotherapy, including CAR-T cell therapy, shows promise but faces challenges in widespread clinical application.
Area of Science:
- Pediatric oncology
- Neuro-oncology
- Cancer immunotherapy
Background:
- Diffuse midline gliomas (DMG) are aggressive pediatric brain tumors with a dismal prognosis.
- Current treatments like surgery, radiation, and chemotherapy offer limited efficacy.
- There is a critical need for novel therapeutic strategies for DMG.
Purpose of the Study:
- To review current immunotherapy-based treatments for diffuse midline gliomas.
- To discuss the limitations and challenges associated with these therapies.
- To highlight recent advancements and future directions in DMG immunotherapy.
Main Methods:
- Review of existing literature on immunotherapy for DMG.
- Exploration of cell-based therapies, oncolytic virotherapy, immune checkpoint inhibition, and vaccination strategies.
- Analysis of clinical trial data, including anti-GD2 CAR-T therapy for diffuse intrinsic pontine glioma (DIPG).
Main Results:
- Immunotherapy represents a promising alternative treatment modality for DMG.
- Anti-GD2 CAR-T therapy has demonstrated recent clinical success in diffuse intrinsic pontine glioma (DIPG) patients.
- Various immunotherapy approaches, including cell-based therapies and checkpoint inhibitors, are under investigation.
Conclusions:
- Immunotherapy offers a potential new avenue for treating diffuse midline gliomas.
- Overcoming challenges in translating preclinical and early-phase clinical data is crucial for effective DMG treatment.
- Continued research and development of novel immunotherapeutic strategies are essential for improving outcomes in pediatric brain tumors.
