Dr. Poul Sorensen, Distinguished Scientist at BC Cancer, in collaboration with Dr. Kevin Hay, Clinician-Ccientist at BC Cancer, and Dr. Wei Li, Assistant Professor at the University of Pittsburgh, received support from the Rutledge Cancer Foundation to develop and optimize novel immunotherapies targeting the surface protein IL1RAP for the treatment of Ewing sarcoma.
Ewing sarcoma, the 2nd most common childhood bone sarcoma, is an aggressive tumor that primarily affects children, adolescents, and young adults. When Ewing sarcoma tumor cells spread to other parts of the body, known as metastasis, survival is drastically diminished to only 15-20%, which has not changed for decades. Immunotherapy (IT) empowers a patient’s own immune system to attack cancer, which has tremendous promise as an alternative to chemotherapies that are often toxic. However, surface proteins suitable for IT targeting are very limited in Ewing sarcoma. It was first recognized nearly 100 years ago that cancer cells exploit distinct pathways to enhance their metabolism (i.e. the use of nutrients to make energy) to support their cancerous features, such as unlimited growth capacity and the ability to spread to other organs. Proteins on the cell surface that help cancer cells maintain their unique metabolic features likely represent an “Achilles heel” for these tumours, which can potentially be exploited as IT targets using antibodies and other targeting techniques. In a recent study, Dr. Sorensen and his team searched for surface proteins that fit the criteria for promising IT targets in Ewing sarcoma. They identified the IL1RAP surface protein as being crucial for helping Ewing sarcoma cells maintain sufficient levels of cysteine, an amino acid metabolite that is critical for Ewing sarcoma cell survival under oxidative stress encountered in the primary tumor microenvironment, and during metastasis. Notably, only minimal IL1RAP is found in normal tissues except placenta, nominating IL1RAP as an ideal IT target with little chance of inducing toxicities in children undergoing treatment for Ewing sarcoma. Throughout this project, they will seek to develop and optimize IT strategies that enhance T cell therapeutic targeting of IL1RAP in Ewing sarcoma. With these approaches, they will develop reagents targeting a key metabolic regulator and driver of metastasis in Ewing sarcoma.