Schultz Liora, McNerney Kevin, Lamble Adam J, Calkoen Friso G, Baruchel Andre, Ceppi Francesco, Curran Kevin J, Gore Lia, Lamb Margaret, Maude Shannon L, Pulsipher Michael A, Qayed Muna, Ramakrishna Sneha, Rheingold Susan R, Rossig Claudia, Silbert Sara K, Steineck Angela, Summers Corinne, Capitini Christian M, Bhojwani Deepa, Gardner Rebecca A, Ghorashian Sara, Shah Nirali N
Division of Pediatric Hematology/Oncology/Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford Medicine, Stanford, CA, USA.
Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Nat Rev Clin Oncol. 2026 Jan 23. doi: 10.1038/s41571-025-01115-w.
Early successes achieved with the CD19-targeted chimeric antigen receptor (CAR) T cell product tisagenlecleucel for the treatment of paediatric B cell acute lymphoblastic leukaemia (B-ALL) led to a historic first FDA approval of a gene therapy. Widespread CAR T cell commercialization followed, along with expansion to other indications and earlier disease settings owing to clear survival benefits. However, commercial development of additional cell therapies for paediatric malignancies has stagnated, despite several products being brought to market as treatments for various haematological malignancies in adults. In contrast to the consistent efficacy achieved across B cell malignancies, CAR T cell approaches have yet to demonstrate durable activity in patients with acute myeloid leukaemia (AML), T cell acute lymphoblastic leukaemia, solid tumours and/or central nervous system cancers, with both biological factors and broader issues of development and access constraining the field. Herein, we showcase the foundational leaps achieved through the initial trials and commercialization of CAR T cell products and contextualize how these early experiences have moulded the field. We review currently approved and investigational CAR T cell therapies for paediatric and young-adult patients, including key considerations regarding safety, access and future directions. We also discuss additional immunotherapy options that guide clinical decision-making regarding optimal utilization of CAR T cells. Although clearly tolerable and efficacious, the CD19-targeted CAR T cell strategy requires ongoing refinement, and research efforts are now geared towards fully exploiting CAR T cells and other immunotherapies to improve survival with broadened access across disease states.
靶向CD19的嵌合抗原受体（CAR）T细胞产品tisagenlecleucel在治疗儿童B细胞急性淋巴细胞白血病（B-ALL）方面取得的早期成功，促成了美国食品药品监督管理局（FDA）对一种基因疗法的历史性首次批准。随后，CAR T细胞广泛商业化，由于其明显的生存益处，适应症扩展到了其他疾病和更早的疾病阶段。然而，尽管有几种产品已作为成人各种血液系统恶性肿瘤的治疗方法推向市场，但用于儿童恶性肿瘤的其他细胞疗法的商业开发却停滞不前。与在B细胞恶性肿瘤中取得的持续疗效不同，CAR T细胞疗法尚未在急性髓系白血病（AML）、T细胞急性淋巴细胞白血病、实体瘤和/或中枢神经系统癌症患者中显示出持久的活性，生物学因素以及开发和可及性等更广泛的问题限制了该领域的发展。在此，我们展示了通过CAR T细胞产品的初步试验和商业化所取得的基础性飞跃，并阐述了这些早期经验如何塑造了该领域。我们回顾了目前已批准的以及正在研究的用于儿科和年轻成人患者的CAR T细胞疗法，包括有关安全性、可及性和未来方向的关键考虑因素。我们还讨论了其他免疫疗法选择，这些选择可为关于CAR T细胞最佳利用的临床决策提供指导。尽管靶向CD19的CAR T细胞策略显然是可耐受且有效的，但仍需要不断完善，目前的研究工作正致力于充分利用CAR T细胞和其他免疫疗法，以提高生存率，并扩大不同疾病状态下的可及性。
