CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Relapsed ALL: CAR T vs transplant vs novel therapies.
Relapsed ALL: CAR T vs transplant vs novel therapies.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
靶向 CD19 的CAR-T 细胞疗法(CAR-T19)拓展了复发/难治性(r/r)B 细胞急性淋巴细胞白血病(ALL)患者的治疗选择。tisagenlecleucel 获批用于儿童及年轻成人 r/r ALL 患者,使部分患者获得了更广泛的治疗机会,但老年患者的治疗(截至本文撰写时)仅在临床试验中可用。不同的 CAR-T19 产品和治疗平台均一致观察到较高的缓解率,但缓解的持久性以及因此巩固性异基因干细胞移植(SCT)的潜在作用则更不确定,且可能因所用产品和治疗人群而异。CAR-T 赋予高缓解率的免疫学特征,也解释了细胞因子释放综合征和免疫效应细胞相关神经毒性综合征这些危及生命的毒性,其严重程度也因患者和疾病特征及产品而异。影响治疗决策的进一步考量包括白细胞单采的可行性及生产时间线、可用的替代治疗方案,以及潜在巩固性异基因 SCT 的适宜性。该领域正在取得进展,以提高缓解率和缓解持续时间并减轻毒性。
Chimeric antigen receptor T-cell therapy targeting CD19 (CART19) has expanded the treatment options for patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). The approval of tisagenlecleucel for pediatric and young adult patients with r/r ALL has allowed broader access for some patients, but the treatment of older adults is available (at the time of this writing) only within a clinical trial.
High remission rates have been consistently observed with varied CART19 products and treatment platforms, but durability of remissions and thus the potential role of a consolidative allogeneic stem cell transplant (SCT) is more uncertain and likely to vary by product and population treated.
The immunologic characteristics of CARTs that confer high response rates also account for the life-threatening toxicities of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, the severity of which also varies by patient and disease characteristics and product.
Further considerations informing a decision to treat include feasibility of leukapheresis and timeline of manufacture, alternative treatment options available, and the appropriateness of a potential consolidative allogeneic SCT. Advances in the field are under way to improve rate and duration of responses and to mitigate toxicity.
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