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The most difficult cases of Ewing sarcoma to treat are when it comes back after completing initial treatment. Dr. Brian Ladle and colleagues at Johns Hopkins University and the National Cancer Institute believe the immune system is capable of mounting a powerful immune response against Ewing sarcoma as an effective treatment. Dr. Ladle and team will identify the best immune targets in Ewing sarcoma and discover ways to activate the immune system against the most promising targets. These targets will be tested in their lab using models.

To make a significant impact for kids fighting Ewing sarcoma, five funding partners have banded together with St. Baldrick’s to support this grant – Advancing Cures for Ewing Sarcoma (ACES) award supported by the Sam Day Foundation, The Faris Foundation, Rutledge Cancer Foundation, The Shohet Family Fund for Ewing Sarcoma Research (a St. Baldrick’s Foundation Hero Fund), and Alan B. Slifka Foundation.

Based on progress to date, Dr. Ladle was awarded a new grant in 2020 to fund an additional year of this Scholar grant. As the Aiden's Army Fund St. Baldrick's Scholar, Dr. Ladle is using the body's own immune system to destroy cancer - specifically a class of cancer in children originating from connective tissues called sarcomas. Using fire as an analogy, Dr. Ladle seeks to build an intense flame of a powerful immune response which will specifically kill the cancer cells. To create this fire, one must follow specific steps. The kindling, which must be easily burned, is protein targets on the cancer cells (termed tumor antigens) recognized by the immune system. Next, the spark to ignite the kindling is initial inflammation in the tumor against these tumor antigens. Finally, to feed the fire, fuel or lighter fluid can be added in the form of recently approved immune modulator drugs which, when infused into patients, bind to immune cells residing in the tumor and activates them to kill the tumor cells. Each ordered step is essential in building an effective fire. This project addresses each of these key aspects for generating a successful immune response to treat sarcomas and creating new tumor antigens, adding inflammation to jump start the immune response against these antigens, and combining with new immune modulators allowing the immune cells to be active in destroying sarcomas.

This grant is funded by and named for the Aiden's Army Fund, a St. Baldrick's Hero Fund. When he was 8 years old, Aiden Binkley was diagnosed with Stage IV rhabdomyosarcoma. He had a huge tumor in his pelvis and the cancer had metastasized to his lungs. But this bright, funny and courageous boy believed he got cancer so he could grow up to find a cure for it. Aiden’s story has inspired so many people and his vision to cure cancer is being carried on by Aiden’s Army through the funding of research. They will march until there is a cure!

Based on progress to date, Dr. Ladle was awarded a new grant in 2015 to fund an optional third year of this fellowship. While the body's immune system is capable of attacking cancer, many factors prevent this from happening. The goal of Dr. Ladle's research is to develop a vaccine to be given to patients that activates their own immune system to treat their cancer. The project focuses on how the body regulates the immune system to normally ignore cancer. New drugs are being developed that could help take the brakes off the immune system and allow it to recognize and attack cancer. Combining these drugs with a cancer vaccine could provide the boost needed for immune therapies to effectively treat pediatric cancers.