Gold September

Pediatric cancers: a European project of more than €13M coordinated by Institut Curie to develop new immunotherapies against Ewing sarcoma

In this Golden month of September dedicated to the fight against pediatric cancers, Institut Curie, the Princess Máxima Center for pediatric oncology and Hopp Children's Cancer Center Heidelberg (KiTZ) announce the launch of the European THEODORA project[1]. It aims to accelerate the development and clinical evaluation of new immunotherapies against Ewing sarcoma, an aggressive cancer that mainly affects adolescents and young adults, and for which current treatments remain insufficient.

Funded with €13.2 million by Horizon Europe Mission Cancer[2] and Fight Kids Cancer[3], this groundbreaking program coordinated by Institut Curie brings together key players in European pediatric research: the Princess Máxima Center for pediatric oncology (the Netherlands), Hopp Children's Cancer Center Heidelberg (Germany), Gustave Roussy, Ghent University Hospital and Ghent University (Belgium) and Childhood Cancer International - Europe (CCI-E).

"This large-scale European project opens up new hope for young patients with Ewing sarcoma by speeding up the development of more precise and more effective treatments against this rare and aggressive tumor," emphasizes Dr Amaury Leruste, pediatric oncologist and researcher[4] at Institut Curie, leader of the THEODORA project. "This unique program demonstrates the strength of Institut Curie: generating innovations at the intersection of research and patient care, and then mobilizing expertise on a European scale to address the challenges of pediatric cancers. This collective approach, aligned with the priorities recently announced by the G7, is crucial for transforming the treatment of these patients.”

From research to clinical trial: a new hope against Ewing sarcoma

The treatment modalities for Ewing sarcoma, the second most common bone tumor in adolescents and young adults, have changed little over the last 25 years. They are based on a combination of chemotherapy, radiotherapy, and surgery. However, the results remain insufficient in the most aggressive forms of the disease.

Institut Curie's pioneering research on Ewing sarcoma is internationally recognized. Led by Dr. Olivier Delattre, director of the SIREDO Center (Care, Innovation, Research in Oncology of Children, Adolescents and young adults) of Institut Curie, this work made it possible to highlight in 1992 the EWS-FLI1 genetic fusion, present in nearly 95% of Ewing sarcomas. Recent research conducted by the groups of Dr. Olivier Delattre, Dr. Joshua Waterfall,[5] and Dr. Olivier Lantz[6] at Institut Curie has led to the identification of unreferenced or "neogenic" genes specific to this tumor, shared by all the patients concerned, and to the filing of two patents relating to the development of targeted immunotherapies, in particular TCR-T cells and therapeutic vaccination. Such neogenes are also observed in other fusion-transcript-positive sarcomas in children and adolescents.

It is in this context that in 2025 the THEODORA project was born, also supported by the recent EU CAN KIDS alliance with the Princess Máxima Center in the Netherlands and the Hopp Children's Cancer Center Heidelberg, Germany. THEODORA aims to implement a European-wide master protocol[7] to facilitate the initiation of early-phase clinical trials evaluating these innovative immunotherapies. Objective: To obtain the first clinical evidence of the efficacy of T-cell based immunotherapies specifically targeting these neogenes in pediatric and adolescent sarcomas, beginning with Ewing sarcoma.

€13.2 million to launch the first two clinical studies, beginning in 2028

The THEODORA program consists of two main projects. The first, dedicated to TCR-T cell therapies, will launch in September 2026. The €8.7 million awarded under the 2025 Horizon Europe Mission Cancer call for projects will enable the launch of the first clinical trial evaluating TCR-T cells targeting a specific neoantigen associated with Ewing sarcoma. These cells were identified by the team of Dr. Olivier Lantz and developed by the teams of CellAction, the cell and gene therapy platform of the Paris Saclay Cancer Cluster (PSCC) at Institut Curie. "Unlike CAR-T cells, which only recognize proteins present on the surface of tumor cells, TCR-T cells can target antigens located inside cancer cells. This specificity paves the way for precise and effective immunotherapies," explains Dr Amaury Leruste.

"THEODORA illustrates our vision of an innovation that places young people with Ewing sarcoma at the heart of each step. At the Princess Máxima Center, we will manufacture TCR-T cells in our GMP platform to guarantee production that meets the highest quality standards. At the same time, our expertise in Patient Reported Outcome Measures[8] (PROMs) will make it possible to integrate the voice of young patients into clinical evaluation, in order to assess not only the effectiveness of treatments, but also their impact on the quality of life," states Dr Miranda Dierselhuis, pediatric oncologist and researcher at the Princess Máxima Center for pediatric oncology.

"Biomarkers allow us to track the disease in real time and understand how each patient responds to treatment. By combining TCR-T cell monitoring, circulating tumor DNA analysis (ctDNA), and immunological monitoring, THEODORA will contribute to developing an ever more effective precision medicine for young patients with sarcomas," explains Dr Christian Seitz, oncologist and researcher at the Hopp Children's Cancer Center Heidelberg (KiTZ).

The second project will begin in 2027 with the launch of a second clinical trial, THEODORA-B, based on a therapeutic vaccine. The €4.5 million in funding secured through Fight Kids Cancer’s 2025 call for projects will enable the evaluation of a ready-to-use messenger RNA vaccine. Its sequence comprises several neoantigens specific to Ewing sarcoma and covers the diversity of HLA profiles[9] among patients with the disease. This vaccine is being developed by Ghent University and Ghent University Hospital in Belgium, in close collaboration with Institut Curie and other partners. The goal is to train the immune system to prevent recurrence in high-risk patients.

Coordinated by Institut Curie, the projects THEODORA and THEODORA-B bring together leading European players, researchers, clinicians, and a patient association to accelerate the development of new immunotherapies for pediatric sarcomas.

Institut Curie, the Princess Máxima Center, the Hopp Children's Cancer Center Heidelberg (KiTZ) and Gustave Roussy, members of the European network Innovative Therapies for Children with Cancer (ITCC), bring their expertise in early clinical trials. The generated data will be managed in accordance with the FAIR principles, in conjunction with BBMRI-ERIC—the European research infrastructure for biobanking and biomolecular resources —and European initiatives such as UNCAN.eu. Their involvement will streamline compliance with EU data standards while facilitating the sharing and reuse of project data. Patient representatives at CCI Europe will be involved at every stage of the project to ensure that the needs of children, adolescents, and their families are taken into account.

The THEODORA project is part of the "Diagnosis and Treatment – ​​Innovative Clinical Trials for Pediatric Cancers" cluster of the European Union's Mission on Cancer, alongside two other projects: EPICA-DIPG (coordinated by the Sant Joan de Déu Research Institute) and PHOENIX (coordinated by the Vall d'Hebron Research Institute – VHIR).