NEWTargets is a research program aimed at using immunotherapy to target neoproteins specific to Ewing’s sarcoma, in order to cure children and adolescents suffering from this type of disease more effectively.
Childhood Sarcomas
Ewing sarcoma is the second most common malignant bone tumor after osteosarcoma in adolescents and young adults. Ewing sarcoma affects approximately 80 to 100 new patients per year in France. The majority of cases (70%) occur in young people aged 5 to 25 years. However, these tumors can be diagnosed before age 5 and after age 30.
The majority of Ewing sarcomas develop in bone, but 15% can develop independently of a bone.
About NEWTargets
The main objective of this project is to develop new therapies for children, adolescents, and young adults affected by Ewing sarcoma (EwS). Despite improvements in treatments over recent decades, one-third of patients succumb due to relapses of the disease that cannot be controlled by conventional therapies. In fact, while the chances of survival for patients without metastasis at diagnosis reach 85% today, survival rates drop dramatically to 20-30% in the case of lung metastases and to less than 5% in the case of bone metastases. Maximizing treatment intensity has not improved survival but has instead increased toxicity and led to mutilating surgeries, such as the amputation of affected limbs. Innovative, more effective, and particularly less toxic treatment options are needed for these patients.
It has been recently demonstrated that EwS is characterized by the production of “neotranscripts,” a genetic anomaly producing abnormal proteins that are the cause of the cancer. Through advanced genetic analyses, researchers will determine the quantity and nature of the different neoproteins produced in EwS, their carcinogenic functions, and how to target them, particularly through immunotherapy. These would indeed constitute exceptional targets because they are produced only in tumor cells and are not found in any healthy tissue in the body.
This project combines the expertise of three leading cancer research centers in Europe (KiTZ in Heidelberg, PMC in Utrecht, Institut Curie in Paris). Advanced genome and proteome sequencing technologies, bioinformatics tools, and functional experiments are employed. If successful, and thanks to ongoing collaboration with immuno-oncologists at the involved centers, the results of this project could be immediately transferred to clinical trials, for example, through a peptide or mRNA vaccination strategy, the implementation of therapeutic antibodies, or the production of CAR-T cells.
Project Progress
To date, 60 tumor extracts have been studied, and their mRNA and neoprotein expression profiles have begun to be characterized. They have also started studying the mechanisms that would allow disrupting the production of these neoproteins.
Summary of the NEWTargets Project
- Lead Investigators: Dr. Sebastian van Heesch
- Program Duration: January 2023 – January 2025
- Countries Involved: Netherlands, France
- Funding by Fight Kids Cancer: €500,000
