PDF(Pubmed)
Abstract：
Bispecific antibodies (BsAbs) are artificially engineered antibodies that can bind simultaneously to the CD3 subunit within the T-cell receptor complex and an antigen on tumor cells, leading to T-cell activation and tumor cell killing. BsAbs against BCMA or GPRC5D have shown impressive clinical activity in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), with some agents having already received regulatory approval after the third (by the European Medicines Agency, EMA) or fourth (by the Food and Drug Administration, FDA) line of therapy; the results of early-phase clinical trials targeting FcRH5 are also promising. Overall, BsAbs as monotherapy correlated with an ORR that exceeded 60%, with a high CR rate ranging between 25% and 50% and a median PFS of around 1 year among patients with a median of 4-6 prior lines of therapy. The main toxicities include cytokine release syndrome, cytopenias, hypogammaglobulinemia, and infections; on-target off-tumor adverse events involving the skin, mucosa, hair, and nails may also occur with anti-GPRC5D BsAbs. Active research to increase their efficacy and improve their tolerance is still in progress, including combination therapies and application in earlier treatment lines and the development of novel agents. A better understanding of the mechanisms of resistance is a challenge and could lead to more personalized approaches.
摘要：
双特异性抗体（BsAb）是人工工程化的抗体，可以同时结合T细胞受体复合物内的CD3亚基和肿瘤细胞上的抗原，导致T细胞活化和肿瘤细胞杀伤。针对BCMA或GPRC5D的BsAb在复发/难治性多发性骨髓瘤（RRMM）的大量预处理患者中显示出令人印象深刻的临床活性，一些代理商在第三次之后已经获得了监管机构的批准(由欧洲药品管理局，EMA)或第四(由食品和药物管理局，FDA）的治疗路线；针对FcRH5的早期临床试验的结果也很有希望。总的来说,BsAb作为单一疗法与超过60%的ORR相关，在中位数为4-6个先前治疗线的患者中，高CR率在25％至50％之间，中位数PFS约为1年。主要毒性包括细胞因子释放综合征，血细胞减少,低球蛋白血症,和感染；涉及皮肤的靶肿瘤外不良事件，粘膜，头发,和指甲也可能发生与抗GPRC5DBsAb。积极研究增加其疗效和提高其耐受性仍在进行中,包括联合疗法和在早期治疗线上的应用以及新型药物的开发。更好地理解抗性机制是一个挑战，可能会导致更个性化的方法。
