肿瘤细胞治疗研究
英文原题：Pediatric AML CAR T cell therapy.
急性髓系白血病（AML）是儿童中第二常见的白血病。
急性髓系白血病（AML）是儿童中第二常见的白血病。尽管数十年来生存率有所改善，但对于高危或化疗难治性 AML 患者，造血干细胞移植（HSCT）仍是唯一的治愈性疗法。HSCT 通过移植物抗白血病效应提供免疫介导的残余白血病控制，突显了同种异体免疫反应在使 AML 患儿获得持久缓解中的重要性。嵌合抗原受体（CAR）T 细胞是经基因工程改造的 T 淋巴细胞，其表达合成受体，将抗原识别与 T 细胞激活和共刺激信号结构域结合起来。通过独立于 MHC 识别肿瘤抗原，CAR T 细胞可介导强效细胞毒性。CD19 靶向 CAR T 细胞已改变复发或难治性 B 细胞急性淋巴细胞白血病儿科患者的结局，但将 CAR T 细胞疗法转化应用于 AML 已被证明具有挑战性。本综述总结了迄今为止针对 AML 的 CAR T 细胞的临床经验，重点介绍儿科数据。我们还回顾了在基础与转化研究中已发现的阻碍 AML CAR T 细胞疗法成功转化的障碍。最后，我们讨论了提高疗效的新兴策略，包括先进的 CAR 设计、优化的抗原和患者选择，以及合理的联合方法。
Acute myeloid leukemia (AML) is the second most common leukemia in children. Although survival rates have improved over several decades, for patients with high-risk or chemotherapy-refractory AML, hematopoietic stem cell transplantation (HSCT) remains the only curative therapy. HSCT provides immune-mediated control of residual leukemia through the graft-versus-leukemia effect, underscoring the importance of allogeneic immune responses in achieving durable remission for children with AML. Chimeric antigen receptor (CAR) T cells are genetically engineered T lymphocytes that express synthetic receptors combining antigen recognition with T cell activation and costimulatory signaling domains. By recognizing tumor antigens independently of MHC, CAR T cells can mediate potent cytotoxicity. CD19-directed CAR T cells have transformed outcomes for pediatric patients with relapsed or refractory B cell acute lymphoblastic leukemia but translating CAR T cell therapy to AML has proven challenging. This review summarizes clinical experiences to date with AML-directed CAR T cells, highlighting pediatric data. We also review barriers to successful translation of AML CAR T cell therapy that have been identified in basic and translational studies. Finally, we discuss emerging strategies to improve efficacy, including advanced CAR designs, optimized antigen and patient selection, and rational combination approaches.
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