Washington University School of Medicine, Division of Oncology , St. Louis, MO , USA.
Expert Opin Investig Drugs. 2015 May;24(5):715-24. doi: 10.1517/13543784.2015.1021415. Epub 2015 Mar 4.
Blinatumomab is a bispecific T-cell engager (BiTE) molecule that recruits cytotoxic T cells to target tumor B cells by linking the CD3 and CD19 antigens. Among the various formats of bispecific antibodies developed in the past 50 years, the BiTE class is remarkable for its low effector-to-target ratio, high tissue penetration and singular ability to activate T cells independent of MHC class I presentation or costimulation. Blinatumomab has been studied in patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) and B-precursor acute lymphoblastic leukemia (B-ALL).
This article reviews the current literature on blinatumomab including its pharmacology, preclinical findings, clinical trials in B-cell NHL and, to a lesser extent, Phase II studies in B-ALL. The authors discuss the potential future directions in light of other new competing therapies for NHL and unmet clinical needs in the market.
The recent approval of blinatumomab for B-ALL symbolizes a breakthrough for BiTE technology with prospective application in the targeted therapy of other cancers. Although blinatumomab seems an unlikely option for treating indolent lymphoma due to toxicity, the need for long-term continuous infusion therapy and multiple promising well-tolerated oral agents, it holds promise for aggressive NHL patients whose diseases are refractory to current standard approaches. Larger trials are needed to demonstrate blinatumomab's curative potential in aggressive histologies.
blinatumomab 是一种双特异性 T 细胞衔接器(BiTE)分子,通过连接 CD3 和 CD19 抗原将细胞毒性 T 细胞募集到靶向肿瘤 B 细胞。在过去 50 年开发的各种双特异性抗体形式中,BiTE 类因其低效应器与靶标比例、高组织穿透力和独立于 MHC 类 I 呈递或共刺激激活 T 细胞的独特能力而引人注目。blinatumomab 已在复发或难治性非霍奇金淋巴瘤(NHL)和 B 前体急性淋巴细胞白血病(B-ALL)患者中进行了研究。
本文综述了关于 blinatumomab 的现有文献,包括其药理学、临床前发现、B 细胞 NHL 的临床试验,以及在较小程度上 B-ALL 的 II 期研究。作者根据其他用于 NHL 的新竞争疗法和市场上未满足的临床需求,讨论了未来的潜在方向。
blinatumomab 最近被批准用于 B-ALL 标志着 BiTE 技术的突破,具有在其他癌症的靶向治疗中的应用前景。尽管由于毒性,blinatumomab 似乎不太可能用于治疗惰性淋巴瘤,但对于需要长期连续输注治疗和多种有前途的耐受良好的口服药物的侵袭性 NHL 患者,它具有潜力。需要更大规模的试验来证明 blinatumomab 在侵袭性组织学中的治愈潜力。