Hosse, R.J. (Ralf J.)

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    Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment
    (Elsevier, 2017) Lüoend, R. (Remo); Zabaleta, A. (Aintzane); Hundemer, M. (Michael); Murr, R. (Ramona); Fauti, T. (Tanja); Umaña, P. (Pablo); Seckinger, A. (Anja); Hosse, R.J. (Ralf J.); Harnisch, L.J. (Lydia Jasmin); Moser, S. (Samuel); Grab, A. (Anna); Lipp, S. (Susanne); Vu, M.D. (Minh Diem); Ho, A.D. (Anthony D.); Delgado, J.A. (Jose Antonio); Strein, K. (Klaus); Moreno, L. (Laura); Neuber, B. (Brigitte); Klein, C. (Christian); Bacac, M. (Marina); Hose, D. (Dirk); Paiva, B. (Bruno); Hillengass, J. (Jens); Prosper-Cardoso, F. (Felipe); Delon, C. (Camille); Merino, J. (Juana); Cavalcanti-Adam, E.A. (Elisabetta Ada); Emde, M. (Martina); Gianotti, R. (Reto); San-Miguel, J.F. (Jesús F.); Latzko, M. (Melanie)
    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.