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 . 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[1] and Fight Kids Cancer[2], 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[3] 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,[4] and Dr. Olivier Lantz[5] 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[6] 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.
In certain childhood cancers where treatment options remain limited, innovation becomes even more urgent. Projects like THEODORA not only bring us closer to more effective and less toxic therapies, but also help ensure that scientific progress translates into better treatments and equitable access to innovation for every child and adolescent who needs it.
€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[7] (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[8] 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).
[1] Horizon Europe is the main research and innovation financing program of the European Union. With a budget of around 93.5 billion euros for the period 2021-2027, it supports international collaboration, scientific excellence, and the development of solutions to major global challenges.
[2] Fight Kids Cancer is a European call for projects dedicated to research in pediatric oncology, jointly supported by five organizations committed to the fight against childhood cancers: Imagine for Margo (France), KickCancer (Belgium), Fondation Kriibskrank Kanner (Luxemburg), CRIS Cancer Foundation (Spain, France and United Kingdom) and KiKa (the Netherlands).
[3] Mechanisms of oncogenesis of childhood tumors Unit (CONCERT) (Inserm U1330)
[4] Head of the Integrative Functional Genomics of Cancer team (Inserm U1330 / Translational Research Department) at Institut Curie
[5] Director of the Clinical Immunology Laboratory at Institut Curie
[6] The master protocol is a framework document used mainly in clinical research, making it possible to group several studies, treatments or sub-projects within the same methodological structure in order to simultaneously evaluate different research hypotheses.
[7] PROMs are standardized instruments that directly capture patients’ perspectives on how their disease and the care they receive affect their health and quality of life.
[8] An HLA profile corresponds to the biological identity card of your cells, defined by unique proteins that allow the immune system to recognize what belongs to the body from what is foreign.
About Institut Curie
Institut Curie, the leading French center for the fight against cancer, combines an internationally renowned research center and a state-of-the-art hospital that provides treatment for all cancers, including the rarest ones. Founded in 1909 by Marie Curie, Institut Curie employs 4,000 researchers, physicians, and health professionals across three sites (Paris, Saint-Cloud, and Orsay), all of whom contribute to its three missions of treatment, teaching and research. As a public-interest foundation authorized to receive donations and bequests, Institut Curie relies on donor support to accelerate scientific discovery and improve treatments and quality of life for patients.
To learn more : curie.fr ; LinkedIn, Facebook, Instagram, Bluesky
About the Princess Máxima Center for pediatric oncology
When a child is seriously ill with cancer, only one thing comes first: a cure.
That is why at the Princess Máxima Center for pediatric oncology, we work together every day in a groundbreaking and passionate way to improve the survival rate and quality of life of children with cancer. Now, and in the longer term. Because children still have a whole life ahead of them.
The Princess Máxima Center is a research hospital, the largest pediatric cancer center in Europe. All children with cancer in the Netherlands are treated here. Our mission: To cure every child with cancer, with optimal quality of life. Over 450 researchers and 900 healthcare professionals work closely with Dutch and international hospitals on better treatments and new perspectives on cures.
In the Princess Máxima Center, Utrecht, Netherlands, the best healthcare professionals and scientists work together on a unique mission: to cure every child with cancer, with optimal quality of life. A mission that remains urgent, as one in four children with cancer dies, and many children who do survive experience the effects of radical treatments throughout their lives.
About Hopp Children’s Cancer Center Heidelberg (KiTZ)
The “Hopp Children’s Cancer Center Heidelberg” (KiTZ) is a pediatric oncology institution of the German Cancer Research Center, Heidelberg University Hospital, and Heidelberg University. Like the National Center for Tumor Diseases (NCT) Heidelberg, which focuses on adult oncology, KiTZ is modeled in structure and concept on the U.S. model of so-called “Comprehensive Cancer Centers” (CCC). KiTZ is both a treatment and research center for oncological and hematological diseases in children and adolescents. Its goal is to scientifically investigate the biology of childhood cancers and severe blood disorders and to closely link promising research approaches with patient care – from diagnosis and treatment through to follow-up care. Children with cancer, especially those for whom no established treatment options are available, receive an individual treatment plan at KiTZ, developed jointly by experts from various disciplines in tumor boards. Many young patients are able to participate in clinical trials and thus gain access to new treatment options. In translating research findings from the laboratory into the clinic, KiTZ therefore plays a pioneering role.
List of THEODORA project partners
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THEODORA: Institut Curie
Funded by the European Union[1]. |
THEODORA-B:
Institut Curie
Funded by Fight Kids Cancer |
[1] Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the European Executive Agency for Health and Digital Technology (HaDEA). Neither the European Union nor the granting authority can be held responsible for them.