GD2: hopes and challenges for the treatment of pediatric patients with tumors of the central nervous system

Pediatric Central Nervous System (CNS) tumors are the leading cause of cancer-related death in children, yet effective treatment options remain limited. The tumor-associated antigen GD2 is a promising target for immunotherapeutic approaches aimed at treating pediatric CNS cancers; however, its heterogeneous expression within and between tumors can complicate the development of effective strategies. Here we review different aspects of GD2 biology, including its structure, synthesis pathway, and cellular and tissue expression, focusing on pediatric CNS tumors. We provide a detailed overview of the investigational and diagnostic methods for evaluating GD2 expression on freshly dissociated tumor samples, tissue sections, or tumor-derived cell lines, and as a circulating marker in liquid biopsy. Furthermore, we provide a comprehensive overview of GD2-based therapeutic strategies, such as monoclonal antibodies, CAR T-cells, aptamers, vaccines, and multimodal approaches, from preclinical studies to recent clinical applications, highlighting both the promise and challenges of targeting GD2 in these cancers.