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Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment
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 ,
Minh Diem Vu
March 2017
March 2017
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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.