title: Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment.
abstract: We identified B cell maturation antigen (BCMA) as a potential therapeutic target in 778 newly diagnosed and relapsed myeloma patients. We constructed an IgG-based BCMA-T cell bispecific antibody (EM801) and showed that it increased CD3+T cell/myeloma cell crosslinking, followed by CD4+/CD8+T cell activation, and secretion of interferon-γ, granzyme B, and perforin. This effect is CD4 and CD8 T cell mediated. EM801 induced, at nanomolar concentrations, myeloma cell death by autologous T cells in 34 of 43 bone marrow aspirates, including those from high-risk patients and patients after multiple lines of treatment, tumor regression in six of nine mice in a myeloma xenograft model, and depletion of BCMA+cells in cynomolgus monkeys. Pharmacokinetics and pharmacodynamics indicate weekly intravenous/subcutaneous administration.
authors.affiliation: Universitätsklinikum Heidelberg, Labor für Myelomforschung and Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Seckinger
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, IDISNA, Avda. Pío XII, 55, 31008 Pamplona, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Delgado
authors.affiliation: Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Moser
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, IDISNA, Avda. Pío XII, 55, 31008 Pamplona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Moreno
authors.affiliation: Universitätsklinikum Heidelberg, Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Neuber
authors.affiliation: Universitätsklinikum Heidelberg, Labor für Myelomforschung and Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Grab
authors.affiliation: Universitätsklinikum Heidelberg, Labor für Myelomforschung and Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lipp
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, IDISNA, Avda. Pío XII, 55, 31008 Pamplona, Spain.
authors.forename: Juana
authors.initials: J
authors.lastname: Merino
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, IDISNA, Avda. Pío XII, 55, 31008 Pamplona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
authors.affiliation: Universitätsklinikum Heidelberg, Labor für Myelomforschung and Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Emde
authors.affiliation: Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Camille
authors.initials: C
authors.lastname: Delon
authors.affiliation: Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Latzko
authors.affiliation: Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Gianotti
authors.affiliation: Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Remo
authors.initials: R
authors.lastname: Lüoend
authors.affiliation: Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Ramona
authors.initials: R
authors.lastname: Murr
authors.affiliation: Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Hosse
authors.affiliation: Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Lydia Jasmin
authors.initials: LJ
authors.lastname: Harnisch
authors.affiliation: Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Marina
authors.initials: M
authors.lastname: Bacac
authors.affiliation: Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Fauti
authors.affiliation: Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Klein
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, IDISNA, Avda. Pío XII, 55, 31008 Pamplona, Spain.
authors.forename: Aintzane
authors.initials: A
authors.lastname: Zabaleta
authors.affiliation: Universitätsklinikum Heidelberg, Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Hillengass
authors.affiliation: University of Heidelberg, Institute for Physical Chemistry and Max Planck Institute for Medical Research, 69120 Heidelberg, Germany.
authors.forename: Elisabetta Ada
authors.initials: EA
authors.lastname: Cavalcanti-Adam
authors.affiliation: Universitätsklinikum Heidelberg, Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Universitätsklinikum Heidelberg, Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hundemer
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, IDISNA, Avda. Pío XII, 55, 31008 Pamplona, Spain.
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San Miguel
authors.affiliation: EngMab AG, 8808 Pfäffikon, Switzerland.
authors.forename: Klaus
authors.initials: K
authors.lastname: Strein
authors.affiliation: Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Pablo
authors.initials: P
authors.lastname: Umaña
authors.affiliation: Universitätsklinikum Heidelberg, Labor für Myelomforschung and Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: dirk.hose@med.uni-heidelberg.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, IDISNA, Avda. Pío XII, 55, 31008 Pamplona, Spain. Electronic address: bpaiva@unav.es.
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.affiliation: EngMab AG, 8808 Pfäffikon, Switzerland. Electronic address: dv@engmab.com.
authors.forename: Minh Diem
authors.initials: MD
authors.lastname: Vu
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000096:biosynthesis / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D053301:B-Cell Maturation Antigen / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008252:Macaca fascicularis; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D018033:Antibodies, Bispecific; D053301:B-Cell Maturation Antigen
keywords: BCMA; T cell bispecific antibody; immunotherapy; multiple myeloma; redirected cell killing