Developing CAR T-Cell Therapies for Pediatric Solid Tumors.

Abstract

Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematological malignancies, inducing notable and durable clinical responses. However, for solid tumors, including but not limited to pediatric tumors, several peculiar biological features posed substantial challenges for achieving comparable results. Despite sound pre-clinical evidence of the ability of CAR T cells to eradicate solid malignancies, their activity remains suboptimal when facing the in vivo complexity of solid tumors, characterized by antigen heterogeneity, scarce T-cell infiltration, and an immunosuppressive microenvironment. Neuroblastoma was amongst the first tumors to be evaluated as a potential candidate for GD2-targeting CAR T cells, which recently documented promising results in high-risk, heavily pre-treated patients. Moreover, innovative engineering strategies for generating more potent and persistent CAR T cells suggest the possibility to reproduce, and potentially improve, these promising results on a larger scale. In the next years, harnessing the full therapeutic potential of CAR T cells and other immunotherapeutic strategies may open new possibilities for effectively treating the most aggressive forms of pediatric tumors.