Gökbuget Nicola
Department of Medicine II, University Hospital Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany.
Recent Results Cancer Res. 2020;214:71-91. doi: 10.1007/978-3-030-23765-3_2.
Bispecific T cell engagers are antibody constructs directed to a tumor-specific target on the one hand and to CD3-positive T cells on the other hand. Blinatumomab is a compound with specificity for the pan-B cell marker CD19. Clinical activity was tested in relapsed and refractory (R/R) non-Hodgkin's Lymphoma (NHL), R/R acute lymphoblastic leukemia (ALL), and ALL patients with minimal residual disease. Trials have already been started in de novo ALL. The most clinically relevant toxicities are neurologic events and cytokine release syndrome as with other T cell-activating therapies. The mechanisms of resistance are not fully understood. Higher leukemia load and later stage disease represent unfavorable factors. Besides, an upregulation of regulatory T cells and inhibitory molecules like PD-1/PD-L1 may have a role as the loss of target by several mechanisms. The future will show whether the use of bispecifics in ALL can change the standard treatment algorithms and whether bispecific T cell engagers will also be successfully used in other malignant entities.
双特异性T细胞衔接器是一种抗体构建体，一方面靶向肿瘤特异性靶点，另一方面靶向CD3阳性T细胞。博纳吐单抗是一种对泛B细胞标志物CD19具有特异性的化合物。已在复发难治性（R/R）非霍奇金淋巴瘤（NHL）、R/R急性淋巴细胞白血病（ALL）以及微小残留病的ALL患者中测试了其临床活性。针对初治ALL的试验已经启动。与其他T细胞激活疗法一样，最具临床相关性的毒性是神经事件和细胞因子释放综合征。耐药机制尚未完全明确。较高的白血病负荷和疾病晚期是不利因素。此外，调节性T细胞和抑制分子如PD-1/PD-L1的上调可能通过多种机制导致靶点丢失而发挥作用。未来将表明双特异性药物在ALL中的使用是否会改变标准治疗方案，以及双特异性T细胞衔接器是否也能成功用于其他恶性实体。
