Brain scan of a child with a DIPG tumor, located in the brain stem. Image courtesy of Rishi Lulla, MD, Northwestern University Feinberg School of Medicine and Lurie Children's Hospital of Chicago.
Children with an extremely deadly form of brain cancer might benefit from a new treatment that aims to direct an immune response against a mutant form of a protein found exclusively on cancer cells, according to a new study led by UC San Francisco researchers.
The focus of the study, published online December 4, 2017 in the Journal of Experimental Medicine, is diffuse intrinsic pontine glioma (DIPG), an aggressive pediatric brain cancer. DIPG is rare — estimates suggest that about 300 new cases occur in the United States each year — but almost always fatal.
Because DIPG occurs in a difficult-to-access area of the brain stem that controls vital functions such as breathing, blood pressure, and heart rate, these tumors are almost impossible to remove surgically. Radiation therapy is the current standard treatment, but is rarely effective for long, according to Hideho Okada, MD, PhD, professor of neurological surgery and director of the Brain Tumor Immunotherapy Center at UCSF, and the senior author of the study.
“It is important to develop more innovative treatment approaches for childhood brain cancers, which now are the leading cause of cancer death in children. DIPG is a very deadly type of brain cancer, and not many children survive beyond 12 months from the time of diagnosis.” said Okada, also a member of the Helen Diller Family Comprehensive Cancer Center (HDFCC) at UCSF and of the Parker Institute for Cancer Immunotherapy.
Okada, along with Sabine Mueller, MD, PhD, MAS, an assistant professor of clinical neurology at UCSF and a HDFCCC member, already are leading a phase I clinical trial in children with DIPG and closely related gliomas, in order to evaluate a new anti-tumor vaccine based on the new target identified by Okada’s research group.
The new study’s preclinical results also support the development of an immunotherapy treatment that is potentially more powerful than a simple vaccine, one in which some of the patient’s own immune cells would be genetically engineered to recognize the molecular target, which is found on tumor cells in most cases of DIPG and related gliomas, but not on normal cells.
The immune system needs a boost to fight established tumors. Normally it can distinguish a healthy cell from a cell infected by invading pathogens by inspecting bits of molecules, called antigens, which cells display on their outer surface. Very early in life the immune system learns to tolerate rather than to attack cells displaying antigens made by the body’s own cells. Because tumors arise from our own cells, the immune system is likely to tolerate rather than attack the cells of an established tumor.
The target of the new DIPG treatment is a “neoantigen.” A neoantigen is a fragment of a protein made by a cancer cell that has an abnormal structure — and often an abnormal function — due to genetic mutation, a hallmark of cancer. Researchers are developing techniques to select neoantigens that they think will be the most likely to be seen and identified as foreign by the immune system, and they aim to develop immunotherapies to boost immune responses to tumor cells displaying these neoantigens.