Childhood Brain Cancers
Brain tumors are the most common solid tumors in children. The annual estimated number of new cases is about 30 per million for all childhood brain tumors. Gliomas encompass tumors of the central nervous system, which differ based on the brain’s original cell types (astrocytes or oligodendrocytes or both) and their aggressiveness levels (from least to most aggressive: low-grade glioma, anaplastic glioma, and high-grade gliomas).
Low-grade gliomas (benign) are more common in younger children, while malignant gliomas affect older children or adolescents. These tumors include forms with very good prognoses, such as pilocytic astrocytoma, and diseases that are more challenging to treat, such as diffuse intrinsic pontine glioma.
Learn more about gliomas: link to gliomas article
About the Project
Primary brain tumors have the worst prognosis among pediatric tumors, with current treatment based on radiotherapy and chemotherapy because these tumors are often inoperable. These treatments, rarely curative, induce toxicity due to the sensitivity of this vital organ. The refractory nature of brain tumors to current treatments necessitates urgently developing new therapeutic approaches to improve patients’ quality of life and life expectancy.
Dr. Fougeray’s work fully aligns with these therapeutic innovation programs aimed at increasing treatment efficacy while reducing side effects. Cellular therapy based on genetically modified T lymphocytes to express a chimeric antigen receptor (CAR) has recently been proposed (CAR-T Cells). These drug cells are capable of recognizing and destroying cancer cells and have shown effectiveness in treating chemotherapy-refractory leukemias. However, they need to be optimized for solid tumors given the tumor’s immunosuppressive microenvironment.
The use of a subtype of T lymphocytes, Vγ9Vδ2, targeting the O-acetylated GD2 ganglioside, could represent an effective therapeutic solution while minimizing toxic effects. To conduct a Phase I clinical trial, the project’s objective is to establish preclinical proof of concept of the anti-tumor efficacy of Vγ9Vδ2 CAR-T cells targeting pediatric brain tumors, especially high-grade gliomas with a very bleak prognosis.
Project Progress:
- Started in September 2022
- To validate the efficacy of CAR-T-GD2 lymphocytes, a human pediatric glioblastoma cell line (CHLA-200) and two primary human cultures of diffuse midline gliomas (PBT-22 and PBT-29), all expressing the O-acetylated GD2 ganglioside (GD2OAc), have been selected and characterized.
- Several batches of Vγ9Vδ2 CAR lymphocytes with different CAR-GD2 constructs have been generated.
- Initial in vitro results indicate that CAR-GD2 T cells activate and induce short- and long-term destruction of tumor cells.
- In 2024, CAR-GD2 T cells will be tested in mouse models grafted with high-grade glioma cells (PDX model).
Project Summary
- Promoter: University of Nantes
- Principal Investigator: Dr. Sophie Fougeray
- Program Duration: September 2022 – September 2024
- Countries involved: France
- Funding from Imagine for Margo: €50,000
This trial was co-funded by the Rallye du Cœur de Nantes 2022 and was selected by the SFCE as part of its 2021 call for projects.
