Facing CAR T Cell Challenges on the Deadliest Paediatric Brain Tumours
Cristina Ferreras,
Lucía Fernández,
Laura Clares-Villa,
Marta Ibáñez-Navarro,
Carla Martín-Cortázar,
Isabel Esteban-Rodríguez,
Javier Saceda,
Antonio Pérez-Martínez
Affiliations
Cristina Ferreras
Translational Research in Paediatric Oncology, Haematopoietic Transplantation and Cell Therapy, Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, 28046 Madrid, Spain
Lucía Fernández
Haematological Malignancies H12O, Clinical Research Department, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain
Laura Clares-Villa
Translational Research in Paediatric Oncology, Haematopoietic Transplantation and Cell Therapy, Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, 28046 Madrid, Spain
Marta Ibáñez-Navarro
Haematological Malignancies H12O, Clinical Research Department, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain
Carla Martín-Cortázar
Translational Research in Paediatric Oncology, Haematopoietic Transplantation and Cell Therapy, Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, 28046 Madrid, Spain
Isabel Esteban-Rodríguez
Pathology Anatomy Service, University Hospital La Paz, 28046 Madrid, Spain
Javier Saceda
Department of Paediatric Neurosurgery, University Hospital La Paz, 28046 Madrid, Spain
Antonio Pérez-Martínez
Translational Research in Paediatric Oncology, Haematopoietic Transplantation and Cell Therapy, Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, 28046 Madrid, Spain
Central nervous system (CNS) tumours comprise 25% of the paediatric cancer diagnoses and are the leading cause of cancer-related death in children. Current treatments for paediatric CNS tumours are far from optimal and fail for those that relapsed or are refractory to treatment. Besides, long-term sequelae in the developing brain make it mandatory to find new innovative approaches. Chimeric antigen receptor T cell (CAR T) therapy has increased survival in patients with B-cell malignancies, but the intrinsic biological characteristics of CNS tumours hamper their success. The location, heterogeneous antigen expression, limited infiltration of T cells into the tumour, the selective trafficking provided by the blood–brain barrier, and the immunosuppressive tumour microenvironment have emerged as the main hurdles that need to be overcome for the success of CAR T cell therapy. In this review, we will focus mainly on the characteristics of the deadliest high-grade CNS paediatric tumours (medulloblastoma, ependymoma, and high-grade gliomas) and the potential of CAR T cell therapy to increase survival and patients’ quality of life.
