Detalle Publicación

ARTÍCULO
Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma treatment
Autores: Seckinger A; Delgado García, José Antonio; Moser S; Moreno Narro, Laura; Neuber B; Grab A; Lipp S; Merino Roncal, Juana María; Prosper Cardoso, Felipe; Emde M; Delon C; Latzko M; Gianotti R; Lüoend R; Murr R; Hosse RJ; Harnisch LJ; Bacac M; Fauti T; Klein C; Zabaleta Azpiroz, Aintzane; Hillengass J; Cavalcanti-Adam EA; Ho AD; Hundemer M; San Miguel Izquierdo, Jesús; Strein K; Umaña P; Hose D; Paiva, Bruno; Vu MD
Título de la revista: CANCER CELL
ISSN: 1535-6108
Volumen: 31
Número: 3
Páginas: 396 - 410
Fecha de publicación: 2017
Resumen:
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-gamma, 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.