An anti-B cell maturation antigen bispecific antibody for multiple myeloma

J Am Chem Soc. 2015 Apr 29;137(16):5288-91. doi: 10.1021/jacs.5b01876. Epub 2015 Apr 15.

Abstract

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.

MeSH terms

  • Animals
  • Antibodies, Bispecific / immunology*
  • Antibodies, Bispecific / therapeutic use*
  • B-Cell Maturation Antigen / immunology*
  • Cell Line, Tumor
  • Humans
  • Immunotherapy
  • Mice, SCID
  • Multiple Myeloma / immunology
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology

Substances

  • Antibodies, Bispecific
  • B-Cell Maturation Antigen