From the Division of Pediatric Hematology/Oncology, Department of Pediatrics.
Cancer J. 2021;27(2):119-125. doi: 10.1097/PPO.0000000000000515.
The successful application of chimeric antigen receptor (CAR) T cells for the treatment of relapsed and refractory B-cell malignancies has ushered in a new frontier for the immunotherapy of cancer. Despite its successes, CAR T-cell therapy presents several challenges. Cytokine release syndrome (CRS) triggered by robust and exponential CAR T-cell expansion is the most common adverse effect and may be severe or life-threatening. Although modulation of the interleukin 6 axis was appreciated early on as a means to manage CRS, the exact underlying mechanisms leading to severe CRS remain to be elucidated. What is clear is that severe CRS involves recruitment of the broader immune system into a hyperinflammatory and unregulated state. Myeloid-derived cells appear to play a critical role in this regard and are at the center of active investigation. In this article, we will focus on important elements of CRS, the clinical manifestations, underlying biology, and management strategies including grading, supportive care, and treatment via immunosuppression.
嵌合抗原受体 (CAR) T 细胞在治疗复发和难治性 B 细胞恶性肿瘤方面的成功应用为癌症的免疫治疗开辟了一个新的前沿。尽管取得了成功，但 CAR T 细胞疗法仍存在一些挑战。由强大和指数级 CAR T 细胞扩增引发的细胞因子释放综合征 (CRS) 是最常见的不良反应，可能严重或危及生命。尽管早期人们认识到调节白细胞介素 6 轴是管理 CRS 的一种手段，但导致严重 CRS 的确切潜在机制仍有待阐明。明确的是，严重的 CRS 涉及更广泛的免疫系统招募到一种过度炎症和不受调节的状态。髓样细胞似乎在这方面发挥着关键作用，并且是积极研究的中心。在本文中，我们将重点关注 CRS 的重要元素，包括临床表现、潜在生物学以及管理策略，包括分级、支持性护理和通过免疫抑制治疗。
