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Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma treatment

Summary: 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...

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Hauptverfasser: Seckinger, Anja (VerfasserIn) , Delgado, Jose Antonio (VerfasserIn) , Moser, Samuel (VerfasserIn) , Moreno, Laura (VerfasserIn) , Neuber, Brigitte (VerfasserIn) , Grab, Anna Luise (VerfasserIn) , Lipp, Susanne (VerfasserIn) , Merino, Juana (VerfasserIn) , Prosper, Felipe (VerfasserIn) , Emde-Rajaratnam, Martina (VerfasserIn) , Delon, Camille (VerfasserIn) , Latzko, Melanie (VerfasserIn) , Gianotti, Reto (VerfasserIn) , Lüoend, Remo (VerfasserIn) , Murr, Ramona (VerfasserIn) , Hosse, Ralf J. (VerfasserIn) , Harnisch, Lydia Jasmin (VerfasserIn) , Bacac, Marina (VerfasserIn) , Fauti, Tanja (VerfasserIn) , Klein, Christian (VerfasserIn) , Zabaleta, Aintzane (VerfasserIn) , Hillengaß, Jens (VerfasserIn) , Cavalcanti-Adam, Elisabetta Ada (VerfasserIn) , Ho, Anthony Dick (VerfasserIn) , Hundemer, Michael (VerfasserIn) , San Miguel, Jesus F. (VerfasserIn) , Strein, Klaus (VerfasserIn) , Umaña, Pablo (VerfasserIn) , Hose, Dirk (VerfasserIn) , Paiva, Bruno (VerfasserIn) , Vu, Minh Diem (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2017
In: Cancer cell
Year: 2017, Jahrgang: 31, Heft: 3, Pages: 396-410
ISSN:1878-3686
DOI:10.1016/j.ccell.2017.02.002
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1016/j.ccell.2017.02.002
Verlag, kostenfrei, Volltext: http://www.sciencedirect.com/science/article/pii/S1535610817300168
Volltext
Verfasserangaben:Anja Seckinger, Jose Antonio Delgado, Samuel Moser, Laura Moreno, Brigitte Neuber, Anna Grab, Susanne Lipp, Juana Merino, Felipe Prosper, Martina Emde, Camille Delon, Melanie Latzko, Reto Gianotti, Remo Lüoend, Ramona Murr, Ralf J. Hosse, Lydia Jasmin Harnisch, Marina Bacac, Tanja Fauti, Christian Klein, Aintzane Zabaleta, Jens Hillengass, Elisabetta Ada Cavalcanti-Adam, Anthony D. Ho, Michael Hundemer, Jesus F. San Miguel, Klaus Strein, Pablo Umaña, Dirk Hose, Bruno Paiva, and Minh Diem Vu

MARC

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520 |a Summary: 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. 
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