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An Anti-B Cell Maturation Antigen Bispecific Antibody for Multiple Myeloma

2015; American Chemical Society; Volume: 137; Issue: 16 Linguagem: Inglês

10.1021/jacs.5b01876

1943-2984

Nitya S. Ramadoss, Andrew D. Schulman, Seihyun Choi, David T. Rodgers, Stephanie A. Kazane, Chan Hyuk Kim, Brian R. Lawson, Travis S. Young,

Nanofabrication and Lithography Techniques

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.