A New Approach for DMG Patients

Clinical trials are crucial for understanding the potential effects and benefits of new therapeutics. A recent study led by Dr. Michelle Monje and Dr. Crystal Mackall at Stanford, a GFAC Center of Excellence, describes the results of a phase I clinical trial of a CAR T cell therapy to treat diffuse intrinsic pontine glioma (DIPG) and spinal cord diffuse midline glioma (DMG) tumors.

These CAR T cells utilize a patient’s own immune cells. Once removed they are engineered in the lab to target the GD2 molecule on the surface of DMG cells that possess an H3K27M mutation. GD2 was discovered as a promising target for DIPG/DMG tumors as a result of testing done on autopsy-derived cell cultures from patients with DIPG/DMG. These engineered immune cells are then infused back into the patient to identify and eliminate tumor cells. Major findings from this trial demonstrated safety of CAR T cell therapy for DIPG and spinal cord DMG with intensive monitoring and management, and early evidence of therapeutic response after delivering the CAR T cells intravenously or directly to the brain. Promising early results showed 3 out of 4 patients had reduced tumor burden on MRI scans and improved neurological function following treatment. One patient (shown left) regained a fuller smile and improved walking capacity after CAR T cell infusion.

Understanding how these treatments affect the tumor environment on a cellular and molecular level will inform how the therapy can be improved for future patients. As the trial moves forward, future aims include determining the optimal dose and schedule. We especially thank the brave DMG patients and families, both in and beyond this trial, who donated tissue to inform and advance research on DIPG/DMG and new treatment strategies. While still in early stages, there is reason to hope that better options for treating this devastating disease are on the horizon.

Link to read the full paper: https://www.nature.com/articles/s41586-022-04489-4

Paper Citation: Majzner, R.G., Ramakrishna, S., Yeom, K.W. et al. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature 603, 934–941 (2022). https://doi.org/10.1038/s41586-022-04489-4