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双特异性T细胞衔接器的潜力:博纳吐单抗在急性淋巴细胞白血病中的作用

Potential for bispecific T-cell engagers: role of blinatumomab in acute lymphoblastic leukemia.

作者信息

Le Jeune Caroline, Thomas Xavier

机构信息

Hospices Civils de Lyon, Hematology Department, Lyon-Sud Hospital, Pierre Bénite, France.

出版信息

Drug Des Devel Ther. 2016 Feb 18;10:757-65. doi: 10.2147/DDDT.S83848. eCollection 2016.

DOI:10.2147/DDDT.S83848
PMID:26937176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4762579/
Abstract

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.

摘要

复发/难治性(R/R)B前体急性淋巴细胞白血病(ALL)患者以及治疗期间微小残留病持续存在的患者无白血病生存期较差。尽管一线治疗有所改善,但这些患者的预后仍然很差,尤其是复发后。由于尚无治疗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在ALL治疗中占据了前沿地位。最近,已开发出针对B系原始细胞中表达的特定抗原的单克隆抗体。在这种情况下,CD19备受关注,因为该抗原在B系细胞中表达。因此,它已被选为双特异性T细胞衔接抗体博纳吐单抗的靶抗原。这种精密的抗体结合CD19和CD3的位点,导致T细胞增殖和活化以及B细胞凋亡。由于其血清半衰期短,博纳吐单抗一直通过持续静脉输注给药,安全性良好。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。这种使用博纳吐单抗的新治疗方法已被证明对微小残留病阳性患者和R/R B前体ALL患者有效,经过加速审评程序后最近获得了美国食品药品监督管理局的批准。本综述重点关注博纳吐单抗的概况及其疗效和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d41/4762579/ffd1918286a4/dddt-10-757Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d41/4762579/ffd1918286a4/dddt-10-757Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d41/4762579/ffd1918286a4/dddt-10-757Fig1.jpg

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