肿瘤细胞治疗研究
英文原题：The development of CAR T cells for patients with CNS malignancies.
在过去十年中，嵌合抗原受体（CAR）T细胞已成为某些复发和/或难治性血液系统恶性肿瘤患者的标准治疗手段。
嵌合抗原受体（CAR）T细胞在过去十年中已成为某些复发和/或难治性血液系统恶性肿瘤患者的标准治疗。然而，这种方法在实体瘤患者中很大程度上仍然无效，部分原因是CAR T细胞持久性有限、许多实体瘤具有免疫抑制性肿瘤微环境，以及CAR T细胞向肿瘤内的迁移有限。中枢神经系统（CNS）肿瘤中许多与预后不良相关并需要新的治疗方法，它们带来了额外挑战，例如血脑屏障的存在以及对治疗相关神经毒性的担忧。尽管存在这些困难，涉及原发CNS肿瘤成人和儿童患者的临床试验已显示出疗效信号。在这篇综述中，我们讨论已完成、正在进行和预期开展的在CNS肿瘤患者中测试CAR T细胞的试验。我们还重点介绍最有前景的临床前进展，这些进展可能促成该领域的新临床方法。
Chimeric antigen receptor (CAR) T cells have become standard-of-care therapies for patients with certain relapsed and/or refractory haematological malignancies over the past decade. However, this approach remains largely ineffective in patients with solid tumours, in part owing to limited CAR T cell persistence, the immunosuppressive tumour microenvironment of many solid tumours and limited trafficking of CAR T cells into tumours. Central nervous system (CNS) tumours, many of which are associated with a poor prognosis and require new treatment approaches, present additional challenges such as the presence of the blood-brain barrier as well as concerns over treatment-related neurotoxicities. Despite these difficulties, clinical trials involving both adult and paediatric patients with primary CNS tumours have provided signals of efficacy. In this Review, we discuss completed, ongoing and anticipated trials testing CAR T cells in patients with CNS tumours. We also highlight the most promising preclinical developments that might lead to novel clinical approaches in this area.
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