title: 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.affiliation: †California Institute for Biomedical Research, 11119 North Torrey Pines Road, Suite 100, La Jolla, California 92037, United States.
authors.forename: Nitya S
authors.initials: NS
authors.lastname: Ramadoss
authors.affiliation: †California Institute for Biomedical Research, 11119 North Torrey Pines Road, Suite 100, La Jolla, California 92037, United States.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Schulman
authors.forename: Sei-hyun
authors.initials: SH
authors.lastname: Choi
authors.affiliation: †California Institute for Biomedical Research, 11119 North Torrey Pines Road, Suite 100, La Jolla, California 92037, United States.
authors.forename: David T
authors.initials: DT
authors.lastname: Rodgers
authors.affiliation: †California Institute for Biomedical Research, 11119 North Torrey Pines Road, Suite 100, La Jolla, California 92037, United States.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Kazane
authors.affiliation: †California Institute for Biomedical Research, 11119 North Torrey Pines Road, Suite 100, La Jolla, California 92037, United States.
authors.forename: Chan Hyuk
authors.initials: CH
authors.lastname: Kim
authors.forename: Brian R
authors.initials: BR
authors.lastname: Lawson
authors.affiliation: †California Institute for Biomedical Research, 11119 North Torrey Pines Road, Suite 100, La Jolla, California 92037, United States.
authors.forename: Travis S
authors.initials: TS
authors.lastname: Young
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology* / Q000627:therapeutic use*; D053301:B-Cell Maturation Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D007167:Immunotherapy; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D018033:Antibodies, Bispecific; D053301:B-Cell Maturation Antigen