Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.
This review summarizes advances, barriers, and emerging CAR-T engineering, delivery, and combination strategies for pediatric solid tumors while emphasizing that efficacy and long-term safety remain unestablished.
Open original publication →What the AI sees
This review summarizes advances, barriers, and emerging CAR-T engineering, delivery, and combination strategies for pediatric solid tumors while emphasizing that efficacy and long-term safety remain unestablished.
Research significance
The record reports that antigen heterogeneity, antigen escape, T-cell exhaustion, physical barriers, immunosuppressive tumor microenvironments, and toxicity constrain CAR-T therapy; it is plausible—but not demonstrated here—that improved targets, CAR designs, delivery methods, genetic engineering, or rational combinations could enhance efficacy and safety in pediatric solid tumors.
Source abstract
Chimeric antigen receptor (CAR)-T cell therapy has demonstrated substantial clinical efficacy in pediatric hematologic malignancies; however, its application in pediatric solid tumors remains investigational and is constrained by substantial biological and clinical challenges. Key barriers comprise tumor heterogeneity, antigen escape, T-cell exhaustion, physical barriers and immunosuppressive tumor microenvironment, treatment-related toxicities, and pediatric-specific considerations, including optimal dosing and potential long-term developmental sequelae. Ongoing research focuses on identifying novel target antigens, optimizing CAR architectures, genetically engineering CAR-T cells, and improving delivery strategies to address these barriers. In this review, we summarize recent advances, persistent challenges, and emerging strategies for CAR-T cell therapy in pediatric solid tumors. We also discuss rational combination strategies involving CAR-T cell therapy with chemotherapy, radiotherapy, and immune checkpoint inhibitors aimed at improving therapeutic efficacy and safety. As the field continues to evolve, advances in CAR-T cell therapy may expand therapeutic options for pediatric solid tumors, although further clinical investigation is required to establish its long-term efficacy and safety.