Researchers are learning more about how to harness the immune system to find new treatment options for deadly brain cancer that strikes young children.
Diffuse intrinsic pontine glioma, or DIPG, tumors can’t be surgically removed due to their location on a critical structure of the brain called the brain stem. In addition, because of the presence of the blood-brain barrier, these tumors do not respond well to chemotherapy. Radiation is the most common treatment but it’s temporary, because the tumor grows back, and it isn’t the ideal option for the young, developing brains of small children.
DIPG cells (green) are surrounded by reactive astrocytes (yellow/red) in this image of a model of a pediatric brainstem glioma, from the team’s recent publication. Image credit: Fernando Nunez.
Some adult brain cancers, though, have responded to efforts to invigorate the immune system against the tumor, and a new study shows similar effects in animal models with one of the mutations that are present in human DIPG.
“Immune-mediated gene therapy may lead us to a safe and effective therapeutic approach for DIPG in the future,” says first author Flor Mendez, Ph.D.
The researchers treated mouse models with DIPG-like tumors in the brain stem, using an immunostimulatory gene therapy called TK/Flt3L to assess whether it would have a positive outcome on survival compared to regular care.
“Together, these therapeutic genes sparked the immune system to recognize and kill the tumor cells,” says Maria G. Castro, Ph.D., co-senior author.
“We found anti-tumor immunity and an increase in anti-tumor specific T cells,” says co-senior author Pedro Lowenstein, M.D., Ph.D. “In this type of brain tumor, there are low numbers of immune cells in the tumor microenvironment, and this approach addresses that shortcoming.”
Additionally, the team found that the immune-mediated gene therapy was well tolerated and did not cause any adverse side effects. They say these results will pave the way for future clinical implementation of this immune-stimulatory gene therapy in DIPG patients at the University of Michigan and beyond.