3B. Exploring CAR-T cell therapy for pediatric brain tumours

Immunotherapy is becoming an important therapeutic tool in oncology today, with chimeric antigen receptor (CAR) T cell therapy being one of the most promising new-generation immunotherapeutic strategies. A clinical study in paediatric diffuse midline glioma (DMG) patients has recently shown that GD2-directed CAR-T cell therapy achieves significant therapeutic benefits for these lethal paediatric brain tumours. However, this therapy can still be improved by combination with other treatment modalities that prevent treatment resistance. Besides, CAR-T cell therapy may also be relevant for other paediatric brain tumours, such as ependymoma.

Interestingly, ‘posterior fossa type A’ (PFA) ependymoma, the most common molecular group of paediatric ependymoma, shares several molecular hallmarks with DMG, like the loss of Histone 3 Lysine 27 (H3K27) methylation. Preliminary results show that PFA ependymomas also express GD2, with even higher expression compared to DMG cultures.

In this project, we aim to test the efficacy of GD2-directed CAR-T cell therapy in ependymoma organoid co-cultures and in patient-derived orthotopic xenograft models. In addition, we propose to further analyse GD2 expression in various other types of paediatric brain tumours to possibly extent the application of GD2 CAR-T treatment to other brain tumour (sub)types. As such, results from this translational project may aid in the development of a clinical trial for a broad group of paediatric brain tumour patients.

Preferred skills for this position:

• candidates with a certificate to work with animals and/or with an immunological background