A new, multi-center European clinical trial, coordinated by the Bambino Gesù Pediatric Hospital in Rome, Italy, is underway to evaluate a novel immunotherapy approach for children with high-risk neuroblastoma, a particularly aggressive childhood cancer. The study will focus on the effectiveness of CAR-T cell therapy, engineered to target the GD2 protein found on tumor cells.
An International Effort to Combat Pediatric Neuroblastoma
Funded by the Veronesi Foundation with a €4.8 million investment, the four-year project involves collaboration between six leading European hospitals: the Bambino Gesù Pediatric Hospital (Rome, Italy), the Gustav Roussy Institute (Villejuif, France), Great Ormond Street Hospital for Children (London, UK), Vall d’Hebron University Hospital (Barcelona, Spain), Charité – University Medicine (Berlin, Germany), and St. Anna Children’s Cancer Research Institute (Vienna, Austria). This international collaboration aims to improve outcomes for children facing this challenging diagnosis.
“The objective of the Veronesi Foundation has always been to increase cure rates and improve the quality of life of children affected by cancer,” stated Paolo Veronesi, President of the Veronesi Foundation. “Support for this European study on high-risk neuroblastoma represents a concrete step in this direction: investing in the most advanced clinical research, promoting international collaboration and making accessible innovative therapies for young patients who do not respond to conventional treatments.”
Understanding High-Risk Neuroblastoma
Neuroblastoma is the most common solid tumor outside of the brain in childhood, accounting for approximately 8% of all pediatric cancers. However, roughly half of children diagnosed with the disease are classified as having high-risk neuroblastoma. Despite intensive treatment regimens, the risk of relapse or treatment resistance remains high, affecting around 50% of these patients.
The current trial specifically aims to confirm the efficacy of GD2 CAR-T cells in patients whose neuroblastoma has proven resistant to, or has recurred after, standard first-line therapies. Initial studies conducted at the Bambino Gesù Hospital have demonstrated promising results, with a response rate of 77% and a manageable toxicity profile.
Franco Locatelli, Full Professor of Paediatrics at the Catholic University of the Sacred Heart and Head of the Pediatric Oncohematology and Cellular and Gene Therapy Area of the Bambino Gesù Pediatric Hospital in Rome, commented, “The data we obtained in the study we initially conducted indicate that, thanks to CAR T cells, You can increase the chances of recovery by 4 times for patients with neuroblastoma who do not respond to conventional treatments.”
If these positive results are confirmed, the goal is to make GD2 CAR-T cell therapy more widely available to children across Europe.
CAR-T Cell Therapy: A New Approach
CAR-T cell therapy is a form of immunotherapy that harnesses the patient’s own immune system to fight cancer. T cells, a type of white blood cell, are collected from the patient and genetically engineered to express a chimeric antigen receptor (CAR). This CAR allows the T cells to recognize and attack cancer cells expressing a specific protein, in this case, GD2. The modified CAR-T cells are then infused back into the patient.
Research published in in Nat Rev Clin Oncol highlights the growing development of CAR T cells for various malignancies, including those affecting the central nervous system. While CAR T cell therapy has become a standard treatment for certain blood cancers, its application to solid tumors like neuroblastoma presents unique challenges.
According to a systematic review published in , approximately 33% of CAR T cell trials currently investigate “next-generation” products incorporating features designed to enhance safety and efficacy. These “multifunctional CAR T cells” represent an evolving area of research.
Future Directions and Potential Impact
The study aims to establish a new standard of care for children and adolescents with high-risk neuroblastoma who experience relapse or disease progression after initial treatment. Researchers will investigate the optimal approach to managing these patients, potentially involving sequential administration of different reinduction strategies followed by GD2-CAR-T01 consolidation therapy.
Valentina Gambino, coordinator of research and curation platforms of the Veronesi Foundation, emphasized the significance of the project, stating, “This study represents one of the few multi-centre and international academic projects in its field and will foster collaboration between the institutions involved, promoting the development of cutting-edge technologies for the treatment of this disease.”
the research could have broader implications for the treatment of other cancers, as the GD2 target is also found on the surface of cells in other tumor types, including certain brain tumors, melanoma, retinoblastoma, and bone sarcoma.
The development of effective CAR T cell therapies for solid tumors remains an active area of investigation. Challenges include overcoming the tumor microenvironment, which can suppress T cell activity, and minimizing potential off-target toxicity. Ongoing research, like this European collaborative effort, is crucial to advancing the field and improving outcomes for children with high-risk neuroblastoma and other cancers.
