Immune-based therapies have now been credentialed for pediatric cancers with the robust efficacy of chimeric antigen receptor (CAR) T cells for pediatric B cell acute lymphocytic leukemia (ALL), offering a chance of a cure for children with previously lethal disease and a potentially more targeted therapy to limit treatment-related morbidities. The developmental origins of most pediatric cancers make them ideal targets for immune-based therapies that capitalize on the differential expression of lineage-specific cell surface molecules such as antibodies, antibody-drug conjugates, or CAR T cells, while the efficacy of other therapies that depend on tumor immunogenicity such as immune checkpoint inhibitors has been limited to date. Here we review the current status of immune-based therapies for childhood cancers, discuss challenges to developing immunotherapeutics for these diseases, and outline future directions of pediatric immunotherapy discovery and development.

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