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Bispecific antibodies for cancer therapy: A review
Pharmacology & Therapeutics ( IF 13.5 ) Pub Date : 2017-12-18 , DOI: 10.1016/j.pharmthera.2017.12.002
Anuradha Krishnamurthy , Antonio Jimeno

The ability to produce monoclonal antibodies with defined and distinct specificities has resulted in a vast spectrum of therapeutic monoclonal antibodies including bispecific antibodies (BsAbs). Several types of BsAbs have been produced but the most well-known of these are trispecific antibodies (TrAbs or TrioMabs) and bispecific T cell engager antibodies (BiTE). TrAbs have two variable segments for antigen binding and an Fc component to recruit immune cells. Catumaxomab is a TrAb that has orphan drug status from the Food and Drug Administration (FDA) for EpCam positive gastric and ovarian tumors and was previously approved by the European Medicinal Agency (EMA) for the same indication. One arm of catumaxomab binds to EpCAM, the other binds to CD3 on T cells and the Fc portion recruits immune cells. Catumaxomab is no longer being produced by the manufacturer due to logistic considerations and hence not available in the European market.

Blinatumomab is a BiTE that comprises of two variable segments only with one arm binding to CD19 and the other binding to CD3. Blinatumomab has been approved for relapsed or refractory B-cell precursor ALL in adults and children by the FDA.

There are over 50 bispecific antibodies currently on clinical trials for various malignancies and the hope is that in the future many of these, with better understanding of principles and techniques of production, will provide treatment options for many different types of cancer.



中文翻译:

用于癌症治疗的双特异性抗体:综述

产生具有确定的和独特的特异性的单克隆抗体的能力导致了广泛的治疗性单克隆抗体,包括双特异性抗体(BsAbs)。已经生产了几种类型的BsAb,但其中最著名的是三特异性抗体(TrAb或TrioMab)和双特异性T细胞接合抗体(BiTE)。TrAb具有两个可变区用于抗原结合,而Fc成分则可以募集免疫细胞。Catumaxomab是TrAb,具有美国食品和药物管理局(FDA)的孤儿药状态,可治疗EpCam阳性的胃和卵巢肿瘤,并且先前已获得欧洲药物管理局(EMA)批准用于相同的适应症。catumaxomab的一个臂与EpCAM结合,另一臂与T细胞上的CD3结合,而Fc部分募集免疫细胞。

Blinatumomab是一种BiTE,由两个可变段组成,其中只有一个臂与CD19结合,另一个与CD3结合。FDA已批准将Blinatumomab用于成人和儿童的复发性或难治性B细胞前体ALL。

目前,针对各种恶性肿瘤的临床试验中有50多种双特异性抗体,希望是在将来,在更好地理解生产原理和生产技术的情况下,其中许多能够为多种不同类型的癌症提供治疗选择。

更新日期:2017-12-18
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