The French Academy of Medicine recognizes the efficacy of cell-based therapies in the treatment of solid tumors in children and adults and supports the impetus for innovation that their development represents. It draws attention to France’s delays in institutional production, which is the only way to optimize a patient-specific production while remaining financially accessible.
CAR-T cells targeting GD2: a hope for children with neuroblastoma1
Press release from the French Academy of Medicine
March 26, 2025
Neuroblastoma, derived from cells of the sympathetic nervous system, is the most common extra-cranial solid malignant tumor in young children. It accounts for around 15% of pediatric cancer-related deaths. Although recent advances, particularly in immunotherapy, have improved the treatment of these children, the poor overall prognosis of high-risk forms (only 50% relapse-free survival at two years) and the long-term sequelae require new therapeutic approaches. Among these, CAR-T cells (Chimeric Antigen Receptor T-Cells) targeting the GD2 carbohydrate antigen attract a growing interest.
The GD2 antigen is a glycolipid abundantly expressed on the surface of neuroblastoma tumor cells, but only weakly expressed in normal tissues, making it an ideal therapeutic target. GD2 CAR-T cells are thus able to recognize and eliminate tumor cells expressing GD2. A recent Phase 2 study using third-generation GD2 CAR-T cells (GD2-CART01) showed that, among patients who received the recommended dose the safety profile was acceptable, with notably few systemic inflammatory reactions and peripheral neuropathies (1). Overall survival at 3 years was 60%, and event-free survival 36%. These initial positive results led to the development of such therapies under the aegis of the European Medicines Agency.
Many obstacles still limit the development of cell therapies targeting GD2. Firstly, their efficacy may be reduced by the immunosuppressive tissue microenvironment of glioblastoma, which reduces CAR-T cells activity. In addition, tumor cell expression of GD2 may be heterogeneous, which can promote the emergence of resistant cells. Finally, chronic stimulation induces progressive depletion of CAR-T cells, leading to tumor escape (2). A fourth generation of GD2 CAR-T cells secreting interleukin 18 is currently undergoing Phase I trials in Germany (3). 2
Limited access to these therapies is also a major obstacle, as they require patient-specific extemporaneous production by an accredited cell therapy unit at a very high overall cost. Furthermore, the multiplicity of potential tumor targets and CAR-T cell types, leading to different drugs, and the low incidence of pediatric cancers compared to those in adult, considerably limit the potential return on investment and attractiveness for pharmaceutical companies (4).
However, the economic impact of such a treatment, often administered as a single injection, could be considered relative, compared to other treatments administered on a prolonged basis, sometimes for several years. In France, in this context, public research and cell therapy production partners have recently structured themselves into a research consortium on cell and gene therapies (UNITC), accredited in 2024 by the National Cancer Institute (5).
While CAR-T cells targeting GD2 represent a major advance in the fight against pediatric neuroblastoma and, beyond that, potentially against other adult and pediatric cancers expressing GD2, the French Academy of Medicine recommends:
– To continue and increase support for innovation and research in the field of cell therapy, while preserving the specificity of pediatric approaches;
– To develop and fully exploit in France a cell therapy production capacity and, given the financial stakes of CAR-T therapies, to support a public-industrial research partnership model for the production of these rare and specific cell therapies;
– To amend the European legislative framework to facilitate the gradual availability of advanced therapy medicinal products (ATMPs) and accelerate the development of cell-based therapies.
References:
– Del Bufalo F., De Angelis B., Caruana I., et al, Precision Medicine Team-IRCCS Ospedale Pediatrico Bambino Gesù. GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma, N Engl J Med. 2023 Apr 6; 388 (14) :1284-1295
– Brown C.E., Mackall C.L., CAR T cell therapy: inroads to response and resistance, Nat Rev Imuunol, 2019 Feb;19 (2):73-74
– A phase I safety, dose finding and feasibility trial of GD2IL18CART in patients with relapsed or refractory GD2 positive solid cancers, European Clinical Trial (EUCT) number:2022-501725-21-00: abstract at https://euclinicaltrials.eu
– Daems S., Stevens H., Dewatripont M, et al, A novel approach to boost drug development in paediatric oncology. Nat Rev Drug Discov. 2023 Oct;22(10):769-770
– On April 24, 2024, the French National Cancer Institute (INCA) accredited the UNITC national research consortium for cell and gene therapy. This consortium is being developed under the aegis of the Société française d’immunothérapie des cancers (FITC), the Institut Carnot CALYM, the Institut Carnot OPALE, the Société française d’immunologie (SFI) and the DESCAR-T registry. https://www.e-cancer.fr/Institut-national-du-cancer/Appels-a-projets/Appels-a-projets-resultats/ReCAR-Tcells.
1 Press release from the Academy’s Rapid Communication Platform.
CONTACT PRESS : Virginie Gustin +33 (0)6 62 52 43 42 virginie.gustin@academie-medecine.fr ACADÉMIE NATIONALE DE MÉDECINE, 16 rue Bonaparte – 75272 Paris cedex 06 Site : www.academie-medecine.fr / Twitter : @Acadmed
