WINNING

Ewing sarcoma is a rare and aggressive form of bone and soft tissue cancer typically affecting children, adolescents and young adults, with a peak incidence between 10–19 years-old. Although overall survival (OS) for patients with localized disease now approaches 65% to 75%, approximately 20-25% of patients present metastasis at diagnosis and exhibit a 5-year OS lower than 30%. Patients with recurrence have a dismal prognosis. New therapeutic approaches, such as targeted therapy and immunotherapy, are required to improve outcomes for patients with metastatic, refractory or relapsing tumors. Recently, at Institut Curie, we have discovered that the oncogenic chimeric transcription factor EWS::FLI1, found in over 90% of Ewing sarcomas, induces the expression of neotranscripts and thus of neopeptides in tumor cells highly specific to Ewing sarcoma. These results open several translational opportunities to target tumor-specific antigens not founded in normal tissue, which we propose to investigate in our WINNING proposal. Our objectives, in line with the description of the future Cancer Mission topic text, are to evaluate the safety and preliminary efficacy of an immunotherapy approach in high-risk Ewing sarcoma in a phase 1/2 clinical trial, and to develop innovative clinical tools to support the assessment of tumor response to immunotherapy in patients, as well as the monitoring of long-term effects of the treatment. To do so, we have started to establish a consortium built upon a strong foundation of long-standing collaborations and complementary multidisciplinary expertise among four leading European institutions in pediatric cancer research: Institut Curie (France), DKFZ/KiTZ (Germany), Princess Máxima Center (The Netherlands) and Ghent University (Belgium). Additional partners will be invited to join the project to provide additional expertise needed to complement the medical-scientific expertise of the current partners and fulfil all requirements of the Cancer Mission topic, including a patient organization, humanities and social sciences experts and an innovative SME. The WINNING project will integrate recent advances in our understanding of Ewing sarcoma biology and propose a disruptive immunotherapy strategy applicable to most patients, ultimately setting a new standard for the treatment of this cancer and offering renewed hope to children and their families affected by this devastating disease.