†California Institute for Biomedical Research, 11119 North Torrey Pines Road, Suite 100, La Jolla, California 92037, United States.
J Am Chem Soc. 2015 Apr 29;137(16):5288-91. doi: 10.1021/jacs.5b01876. Epub 2015 Apr 15.
The development of immunotherapies for multiple myeloma is critical to provide new treatment strategies to combat drug resistance. We report a bispecific antibody against B cell maturation antigen (BiFab-BCMA), which potently and specifically redirects T cells to lyse malignant multiple myeloma cells. BiFab-BCMA lysed target BCMA-positive cell lines up to 20-fold more potently than a CS1-targeting bispecific antibody (BiFab-CS1) developed in an analogous fashion. Further, BiFab-BCMA robustly activated T cells in vitro and mediated rapid tumor regression in an orthotopic xenograft model of multiple myeloma. The in vitro and in vivo activities of BiFab-BCMA are comparable to those of anti-BCMA chimeric antigen receptor T cell therapy (CAR-T-BCMA), for which two clinical trials have recently been initiated. A BCMA-targeted bispecific antibody presents a promising treatment option for multiple myeloma.
开发用于多发性骨髓瘤的免疫疗法对于提供新的治疗策略以对抗耐药性至关重要。我们报告了一种针对 B 细胞成熟抗原（BiFab-BCMA）的双特异性抗体，它能够有效地将 T 细胞重新定向以裂解恶性多发性骨髓瘤细胞。BiFab-BCMA 裂解靶 BCMA 阳性细胞系的效力比以类似方式开发的靶向 CS1 的双特异性抗体（BiFab-CS1）高 20 倍。此外，BiFab-BCMA 在体外可强烈激活 T 细胞，并在多发性骨髓瘤的原位异种移植模型中迅速介导肿瘤消退。BiFab-BCMA 的体外和体内活性与最近启动的两项临床试验的抗 BCMA 嵌合抗原受体 T 细胞疗法（CAR-T-BCMA）相当。针对 BCMA 的双特异性抗体为多发性骨髓瘤提供了一种有前途的治疗选择。
