A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo

Leukemia. 2017 Aug;31(8):1743-1751. doi: 10.1038/leu.2016.388. Epub 2016 Dec 27.


B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein that is expressed on malignant plasma cells of multiple myeloma (MM) patients and therefore is an ideal target for T-cell redirecting therapies. We developed a bispecific T-cell engager (BiTE) targeting BCMA and CD3ɛ (BI 836909) and studied its therapeutic impacts on MM. BI 836909 induced selective lysis of BCMA-positive MM cells, activation of T cells, release of cytokines and T-cell proliferation; whereas BCMA-negative cells were not affected. Activity of BI 836909 was not influenced by the presence of bone marrow stromal cells, soluble BCMA or a proliferation-inducing ligand (APRIL). In ex vivo assays, BI 836909 induced potent autologous MM cell lysis in both, newly diagnosed and relapsed/refractory patient samples. In mouse xenograft studies, BI 836909 induced tumor cell depletion in a subcutaneous NCI-H929 xenograft model and prolonged survival in an orthotopic L-363 xenograft model. In a cynomolgus monkey study, administration of BI 836909 led to depletion of BCMA-positive plasma cells in the bone marrow. Taken together, these results show that BI 836909 is a highly potent and efficacious approach to selectively deplete BCMA-positive MM cells and represents a novel immunotherapeutic for the treatment of MM.

MeSH terms

  • Animals
  • Antibodies, Bispecific / therapeutic use*
  • Apoptosis
  • B-Cell Maturation Antigen / immunology*
  • CD3 Complex / immunology*
  • Cells, Cultured
  • Cytokines / metabolism
  • Female
  • Humans
  • Lymphocyte Activation
  • Macaca fascicularis
  • Mice
  • Multiple Myeloma / immunology
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy*
  • T-Lymphocytes / immunology*
  • Xenograft Model Antitumor Assays


  • Antibodies, Bispecific
  • B-Cell Maturation Antigen
  • CD3 Complex
  • Cytokines