RESEARCHER SPOTLIGHT: MICHELLE MONJE-DEISSEROTH, MD, PhD
Recognizing the emerging gap in support for new clinical trials, the ChadTough Defeat DIPG Foundation funded a pilot grant to Dr. Michelle Monje-Deisseroth of Stanford University. Awarded last May, the grant allowed Dr. Monje to employ a clinical fellow, Dr. Jasia Mahdi, to assist in her CAR T-cell clinical trial.
Dr. Mahdi is a pediatric neurologist who has just completed her pediatric neuro-oncology fellowship. During that fellowship year, Dr. Mahdi took a keen interest in the GD2 CAR T-cell trial. She stepped in to help with subject screening, joined the regular clinical operations meetings, participated in the clinical care of the trial patients, and became involved in the planning and design of the next stage of the trial. Already a key part of the trial team, with a keen interest in immunotherapy for children with brain tumors, it was a perfect fit for Dr. Mahdi to stay on for a year and immerse herself in pediatric neuro-immuno-oncology.
In a recent interview with Dr. Monje, we learned more about the CAR T-cell clinical trial, how it might be promising for DIPG patients, and the important role the grant has played in conducting this exciting work.
CTDDF: CAN YOU DESCRIBE THE CAR T-CELL TRIAL AND HOW IT WORKS?
Dr. Monje: In our past laboratory work, we discovered that DIPG cells express a very high level of a molecule called GD2 on the surface of the cancer cells. This was an exciting discovery because GD2 serves as a good target for the immune system to attack DIPG, if it is trained to do so. We tested the potential of chimeric antigen receptor (CAR) T cells that recognize GD2 against DIPG in mice, and found that this cleared DIPG tumors in mice. In the CAR T-cell trial, we take a child’s own T cells and express GD2-targeting CARs in them, essentially giving the child’s immune cells a tool to specifically recognize and fight DIPG tumor cells. Then we give these GD2-targeting CAR T cells back to the child, either through a vein (IV) or directly into the ventricles of the brain. Children are then monitored closely in the hospital during the period of therapeutic inflammation. If anti-tumor benefit to the child is evident, multiple administrations of CAR T cells are offered.
CTDDF: WHAT MAKES YOU EXCITED ABOUT THIS TRIAL?
Dr. Monje: I am excited about the potential of this therapy because of how effective it was in mice with DIPG, and because of the early results of the trial so far. It was a striking and consistent result; after more than a decade of research with DIPG preclinical models, I had never seen anything that promising.
CTDDF: WHAT WILL BE THE ROLE AND RESPONSIBILITIES OF THE CLINICAL FELLOW IN HELPING WITH THE TRIAL?
Dr. Monje: The clinical fellow will be part of the team that conducts the trial and takes care of the trial participants day-to-day. In doing so, the fellow will not only contribute to advancing this new therapy for DIPG, but will also learn how to safely deliver inflammation-causing therapy for brainstem tumors, which requires a specific skill set and knowledge base. The fellow will gain the expertise to deliver and manage immune-based therapies for childhood brain tumors, which is emerging as a new pillar of pediatric oncology.
The CAR T-cell clinical trial has shown great promise, and after decades, could finally offer patients with DIPG a new treatment option for a disease that has historically proven resistant to other therapies. The ChadTough Defeat DIPG Foundation is proud to be supporting this cutting-edge work, and we look forward to following the progress in Dr. Monje’