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博纳吐单抗,一种用于治疗急性淋巴细胞白血病的双特异性抗CD19/CD3双特异性T细胞衔接器(BiTE)抗体:前景与当前儿科应用

Blinatumomab, a Bi-Specific Anti-CD19/CD3 BiTE(®) Antibody for the Treatment of Acute Lymphoblastic Leukemia: Perspectives and Current Pediatric Applications.

作者信息

Hoffman Lindsey M, Gore Lia

机构信息

The Center for Cancer and Blood Disorders, Children's Hospital Colorado, School of Medicine, University of Colorado Cancer Center , Aurora, CO , USA.

出版信息

Front Oncol. 2014 Mar 31;4:63. doi: 10.3389/fonc.2014.00063. eCollection 2014.

Abstract

Leukemia is the most common childhood malignancy and acute lymphoblastic leukemia (ALL) represents the largest sub-type. Despite remarkable improvements over the last 40 years, standard therapy fails in 10-20% of newly diagnosed patients. Survival for children with relapsed ALL is poor, and the development and implementation of novel therapeutic strategies in pediatric ALL are critical to further advancements. Immunotherapeutic approaches have been central to more novel ALL therapies. However, more recent innovation in antibody engineering has improved potency and efficacy, and antibody-drug conjugates (ADCs) are an especially attractive option in severely immunocompromised patients. An even more sophisticated antibody design is that of bi-specific T-cell engaging or BiTE(®) antibodies, which directly recruit effector T cells to augment the anti-neoplastic effect. This review focuses on blinatumomab, a bi-specific anti-CD19/CD3 antibody that has shown efficacy in adult patients with precursor B-ALL and is currently being evaluated in the pediatric setting.

摘要

白血病是儿童期最常见的恶性肿瘤,急性淋巴细胞白血病(ALL)是最大的亚型。尽管在过去40年中有了显著改善,但标准疗法仍有10%-20%的新诊断患者治疗失败。复发ALL患儿的生存率很低,因此在儿科ALL中开发和实施新的治疗策略对于进一步进展至关重要。免疫治疗方法一直是更新的ALL治疗的核心。然而,抗体工程领域的最新创新提高了效力和疗效,抗体药物偶联物(ADC)对于严重免疫功能低下的患者是一种特别有吸引力的选择。一种更为复杂的抗体设计是双特异性T细胞衔接或双特异性T细胞衔接器(BiTE®)抗体,它直接募集效应T细胞以增强抗肿瘤作用。本综述重点关注博纳吐单抗,一种双特异性抗CD19/CD3抗体,已在成人前体B-ALL患者中显示出疗效,目前正在儿科环境中进行评估。

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