St. Baldrick’s Foundation Research Outcomes blogs highlight examples of the progress your donations are supporting. This quarterly edition focuses on research impacting kids with DIPG, Ewing sarcoma, medulloblastoma, and more.
Thank you for making these advances possible.
Repeated CAR T-Cell Treatment For DIPG Patients
Diffuse intrinsic pontine glioma (DIPG) is a deadly brain tumor in kids, with most patients surviving only about 11 months after diagnosis. Researchers know that a protein called B7-H3 is present on many pediatric brain tumors. Recently, the St. Baldrick’s Foundation Empowering Pediatric Immunotherapies for Childhood Cancer (EPICC) Team tested a new treatment using CAR T-cells (a type of immune cell that has been genetically modified to attack cancer) to target that protein.
The research team ran a small phase 1 clinical trial to test whether it was safe and possible to repeatedly deliver B7-H3 CAR T-cells directly into the brain of kids with DIPG and to see how well the treatment spread in the body. They found the treatment was tolerable, the highest planned dose was safe, and incredibly, 3 patients were still alive 44-52 months later.
While these results are promising, research must continue to find ways to achieve these results for more children. A larger follow-up study is being planned at multiple hospitals.
Using Genetic Markers to Guide Ewing Sarcoma Risk Stratification
A recent paper from the Children’s Oncology Group reports on a study that aimed to understand why some patients with localized Ewing sarcoma respond well to treatment while others don’t. Researchers looked at kids treated with current standard therapies and analyzed their genetic data. They found that most patients had a specific gene fusion already known to be associated with Ewing sarcoma (EWS canonical fusion). They also found mutations on TP53 genes, STAG2 genes, or repeated DNA changes in a smaller portion of patients.
When analyzing this data, researchers found that patients with TP53 mutations, STAG2 mutations, or DNA changes were more likely to relapse. However, after more detailed analysis only the STAG2 mutation was a strong indicator of relapse risk. This suggests that STAG2 mutations could predict a higher risk of relapse in kids with Ewing sarcoma. Future work integrating biomarkers into clinical trials may improve risk stratification for kids with Ewing sarcoma. Risk stratification gives doctors the option to offer stronger treatment to those most at risk.
Revealing CAR T-Cells’ Distinct Cancer-Killing Behavior
CAR T-cells are engineered immune cells designed to attack cancer. There are different types of CAR T-cells that work in different ways. Researchers have described the two most common types as “sprinter” and “marathoner” CAR T-cells. The sprinters kill cancer cells quickly and efficiently, but their activity is short-lived, while marathoners kill cancer cells consistently over a longer period.
In a recent study, researchers aimed to understand how these different CAR T-cells work at molecular and cellular levels. They found that these differences are due to how the CAR T-cells organize certain molecules on their surface when they bind to cancer cells. By understanding what is happening at this level, they can engineer CAR T-cells to adapt their killing behaviors to target hard to treat cancers. This may result in treatments that are faster, longer lasting, or a mix of both, depending on what’s needed for different cancers.
St. Baldrick’s Foundation has supported this research in two ways: First, through the St. Baldrick’s Foundation EPICC team, and also through the research being conducted by St. Baldrick’s Fellow Dr. Mohammad Abu Arja, supported by the Be Brooks Brave Hero Fund.
A ‘Game-Changer’ for Medulloblastoma Risk Classification
Medulloblastoma is the most common brain cancer in kids. Researchers divide it into four main groups, but newer research has found many other sub types, some of which are harder to treat. Accurately identifying these subtypes, or risk classification, is important for treatment decisions.
In a recent study, St. Baldrick’s funded researcher Dr. Olivier Ayrault and colleagues, tested a technology called Nanopore sequencing to see if it could correctly identify medulloblastoma subtypes. When comparing it to the current best method, they found that Nanopore sequencing was not only highly accurate, but faster and less expensive. These results suggest Nanopore sequencing could hold significant potential for enhancing patient risk classification.
Not every publication of research supported by St. Baldrick’s makes the news, but each one adds to the body of scientific knowledge that takes us one step closer to better outcomes for kids with cancer. Your continued support will make more research possible to Conquer Kids’ Cancer.
Donate now and help support research into better treatments for kids with cancer.
