Potential for bispecific T-cell engagers: role of blinatumomab in acute lymphoblastic leukemia.
Potential for bispecific T-cell engagers: role of blinatumomab in acute lymphoblastic leukemia.
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DOI：
10.2147/dddt.s83848
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Thomas X
中科院分区：
文献类型：
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作者：
Le Jeune C;Thomas X
复发性/难治性（R/R）B前体急性淋巴细胞白血病（ALL）患者和治疗期间微小残留病持续存在的患者无白血病生存率较差。尽管一线治疗有所改善，但这些患者的结局仍然很差，尤其是复发后。由于没有用于治疗R/R B前体ALL患者的标准化疗方案，基于T细胞的治疗方法最近已成为ALL治疗的前沿。最近，已经开发了单克隆抗体以靶向B系母细胞中表达的特异性抗原。在这种情况下，CD 19是非常感兴趣的，因为这种抗原在B系细胞中表达。因此，选择其作为blinatumomab（一种新型双特异性T细胞增殖抗体）的靶抗原。这种复杂的抗体结合CD 19和CD 3的位点，导致T细胞增殖和活化以及B细胞凋亡。由于Blinatumomab的血清半衰期较短，因此通过持续静脉输注给药具有良好的安全性特征。最显著的毒性是中枢神经系统事件和细胞因子释放综合征。Blinatumomab的这种新治疗方法已被证明在微小残留病阳性患者和R/R B前体ALL患者中有效，因此在加速审查过程后，最近获得了美国食品药品监督管理局的批准。本综述重点关注Blinatumomab的特征及其疗效和安全性。
Patients with relapsed/refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) and patients whose minimal residual disease persists during treatment have a poor leukemia-free survival. Despite improvements in front-line therapy, the outcome in these patients remains poor, especially after relapse. As there are no standard chemotherapeutic regimens for the treatment of patients with R/R B-precursor ALL, T-cell-based therapeutic approaches have recently come to the forefront in ALL therapy. Recently, monoclonal antibodies have been developed to target specific antigens expressed in B-lineage blast cells. In this setting, CD19 is of great interest as this antigen is expressed in B-lineage cells. Therefore, it has been selected as the target antigen for blinatumomab, a new bi-specific T-cell engager antibody. This sophisticated antibody binds sites for both CD19 and CD3, leading to T-cell proliferation and activation and B-cell apoptosis. Owing to its short serum half-life, blinatumomab has been administrated by continuous intravenous infusion with a favorable safety profile. The most significant toxicities were central nervous system events and the cytokine release syndrome. This new therapeutic approach using blinatumomab has been shown to be effective in patients with positive minimal residual disease and in patients with R/R B-precursor ALL leading to a recent approval by the US Food and Drug Administration after an accelerated review process. This review focuses on the profile of blinatumomab and its efficacy and safety.