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

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.

• Authors: Nitya S Ramadoss, Andrew D Schulman, Sei-hyun Choi, David T Rodgers, Stephanie A Kazane, Chan Hyuk Kim, Brian R Lawson, Travis S Young
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 137 Issue 16 Pg. 5288-91 (Apr 29 2015) ISSN: 1520-5126 [Electronic] United States
• PMID: 25826669 (Publication Type: Journal Article)

Chemical References

• Antibodies, Bispecific
• B-Cell Maturation Antigen

Topics

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