{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:48:27Z","timestamp":1768391307099,"version":"3.49.0"},"reference-count":193,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Chimeric antigen receptor (CAR) T-cell therapy has emerged as a groundbreaking treatment for pediatric B-cell acute lymphoblastic leukemia (B-ALL), especially for patients with relapsed or refractory disease. CD19-targeted CAR T cells, such as tisagenlecleucel, have demonstrated high rates of complete remission and long-lasting responses in clinical trials. However, challenges such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), antigen escape, and T-cell exhaustion hinder its broader clinical application. Recent advances aim to overcome these obstacles by using multi-targeted CAR-T constructs (e.g., CD19\/CD22), creating armored CAR-T cells with enhanced cytokine signaling, and developing optimized combination therapies. Next-generation approaches, including universal CAR-T cells and microenvironment-responsive designs, show promise in improving efficacy and safety. Despite these innovations, further research is needed to refine manufacturing processes, reduce costs, and improve long-term outcomes. This review emphasizes the transformative potential of CAR-T therapy for pediatric B-ALL and discusses critical challenges and future directions in the field.<\/jats:p>","DOI":"10.3389\/fonc.2025.1691189","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T06:33:38Z","timestamp":1768372418000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Precision immunotherapy with CAR-T cells in pediatric B-cell acute lymphoblastic leukemia: advances and unanswered 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