Anti-GPRC5D/CD3 Bispecific T-Cell-Redirecting Antibody for the Treatment of Multiple Myeloma

Mol Cancer Ther. 2019 Sep;18(9):1555-1564. doi: 10.1158/1535-7163.MCT-18-1216. Epub 2019 Jul 3.


Although treatment advances over recent decades have significantly improved survival of patients with multiple myeloma, there is still an unmet medical need for more effective treatments. In this study, we identified G-protein-coupled receptor family C group 5 member D (GPRC5D) expression on the surface of malignant cells involved in multiple myeloma, but except for plasma cells and B cells, not at appreciable levels on normal hematopoietic cells and bone marrow progenitors, including hematopoietic stem cells. In addition, we constructed IgG-based anti-GPRC5D/CD3 bispecific T-cell-redirecting antibodies (GPRC5D TRAB), which suppressed the tumor growth of GPRC5D-positive myeloma cells through the activation of T cells in vitro and in vivo in xenograft models. Collectively, these findings suggest that GPRC5D is an antigen specific to multiple myeloma and a potential target of TRAB therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / immunology*
  • Antibodies, Bispecific / therapeutic use
  • Antibody Specificity / immunology
  • CD3 Complex / immunology*
  • CHO Cells
  • Cell Line, Tumor
  • Cricetulus
  • Female
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy
  • Receptors, G-Protein-Coupled / immunology*
  • Tumor Burden / drug effects
  • Tumor Burden / immunology
  • Xenograft Model Antitumor Assays / methods


  • Antibodies, Bispecific
  • CD3 Complex
  • GPRC5D protein, human
  • Receptors, G-Protein-Coupled