Lead Researcher: Dr Bernadette Brennan

Institution: Royal Manchester Children’s Hospital

Collaborating Researchers:

Dr. Pablo Berlanga (Gustave Roussy, Paris)

Dr. Natalie Gaspar (Gustave Roussy, Paris)

Dr. Roberto Luksch (IRCCS Istituto Tumori Milano)

Dr. Claudia Valverde (Vall d’Hebron, Barcelona)

Dr. Cristina Mata (Gregorio Marañón Hospital)

Dr. Lianne Haveman (Princess Máxima Center)

Dr. Laura Kirton (CRCTU University of Birmingham)

Mr. Piers Gaunt (CRCTU University of Birmingham)

Ms. Louise Hopkins (CRCTU University of Birmingham)

Prof. Paul Huang (Institute of Cancer Research, United Kingdom)

Introduction

Ewing sarcoma is a rare bone cancer that mainly affects teenagers and young adults. When the disease has already spread, the prognosis is very poor.

Unfortunately, treatments for metastatic Ewing sarcoma have changed very little in decades and, despite being highly aggressive, they cure only a small number of patients. There is an urgent need for new therapeutic combinations that improve these outcomes.

The Project

This international clinical trial will study, for the first time, the combination of standard chemotherapy with a drug called regorafenib, a targeted therapy that blocks tumour growth.

Up to 150 children from different countries will receive these treatment combinations. The aim is to determine whether this strategy improves survival for patients newly diagnosed with metastatic Ewing sarcoma. If successful, it could become the new international standard treatment for children facing this very serious prognosis.

Lead Researcher: Manav Pathania 

Institution: University of Cambridge 

Collaborating Researchers: 

• Dr. Greg Hannon (University of Cambridge, United Kingdom)  

• Dr. Kirsty Sawicka (University of Cambridge, United Kingdom)  

• Dr. Karin Straathof (UCL Cancer Institute, United Kingdom)  

• Dr. Claudia Kleinman (McGill University, Canada)  

• Dr. Nada Jabado (McGill University, Canada)  

• Dr. Maria Vinci (Bambino Gesù Children’s Hospital, Italy)  

Introduction 

Brain tumors are especially difficult to treat because the immune system does not function the same way inside the brain; in fact, many immune cells have great difficulty entering it. Immunotherapy, which has transformed treatment for other types of cancer, has not shown good results in these tumors. 

The problem is that we still do not fully understand how the immune system is organized and behaves inside the brain when tumors develop. This prevents the development of effective immunological treatments for this type of cancer. 

The Project 

Dr. Pathania will apply advanced computational and mathematical techniques to study how immune system cells are organized in three dimensions within the environment surrounding brain tumors. Using high-resolution digital images from real samples, the team will generate 3D maps showing how immune responses are structured in these tumors. 

This new perspective will make it possible to identify which cellular patterns are associated with stronger or weaker immune responses and will lay the groundwork for new immunotherapy strategies specifically adapted to the brain, potentially far more effective than current treatments. 

Lead Researcher: Dr Christina Halsey 

Institution: University of Glasgow

Collaborating Researchers:

• Dr. Alasdair Duguid (University of Edinburgh, United Kingdom)  

• Prof. Andre Baruchel (Robert Debré University Hospital, Université Paris Cité, France)  

• Dr. Janine Stutterheim (Princess Máxima Center, Netherlands)  

• Dr. Maria Thastrup (Rigshospitalet, University of Copenhagen, Denmark)  

• Dr. Marie-Emilie Dourthe (Robert Debré University Hospital, France)  

• Prof. Katrin Ottersbach (University of Edinburgh, United Kingdom)  

• Dr. Marion Strullu (Robert Debré Hospital, France)  

• Dr. Ed Roberts (CRUK Scotland Institute, United Kingdom)  

• Dr. Montserrat Torrebadell Burriel (Sant Joan de Déu Hospital, Spain)  

• Dr. Sujith Samarasinghe (Great Ormond Street Hospital, United Kingdom)  

• Dr. Sara Ghorashian (UCL Great Ormond Street Institute of Child Health, United Kingdom)  

• Dr. Anna Alonso Saladrigues (Sant Joan de Déu Hospital, Spain)  

• Dr. Nick Jones (Swansea University, United Kingdom)  

• Prof. Maria Ascierto (University of Glasgow, United Kingdom)  

• Dr. Elad Jacoby (Sheba Medical Center, Israel) 

Introduction

The most common childhood leukemia, acute lymphoblastic leukemia (ALL), can sometimes hide in the brain, making it difficult to cure. Current chemotherapy treatments in the bone marrow are highly effective, but they struggle to eliminate cancer cells when they hide in the brain and can also cause serious side effects. 

The most common immunotherapies do not work well in the brain, where the environment prevents immune cells from acting effectively. It is still unclear why these therapies, which are highly effective in the bone marrow, fail to completely eliminate tumors in the brain. 

The Project

Dr. Halsey’s team will analyse the fluid surrounding the brains of children with leukemia to understand why the immune system fails there. They will use laboratory models and cutting-edge technology to study how to improve the effectiveness of immunotherapies in the brain. 

The researchers will also design new immune cells equipped with a cellular “radar” (CAR-T cells) adapted to function powerfully within the nervous system. The goal is to develop safer and more effective immunological treatments that could replace or complement current chemotherapy, leading not only to better outcomes but also to safer therapies.