| Literature DB >> 28262554 |
Anja Seckinger1, Jose Antonio Delgado2, Samuel Moser3, Laura Moreno2, Brigitte Neuber4, Anna Grab1, Susanne Lipp1, Juana Merino2, Felipe Prosper2, Martina Emde1, Camille Delon3, Melanie Latzko3, Reto Gianotti3, Remo Lüoend3, Ramona Murr3, Ralf J Hosse3, Lydia Jasmin Harnisch3, Marina Bacac3, Tanja Fauti3, Christian Klein3, Aintzane Zabaleta2, Jens Hillengass4, Elisabetta Ada Cavalcanti-Adam5, Anthony D Ho4, Michael Hundemer4, Jesus F San Miguel2, Klaus Strein6, Pablo Umaña3, Dirk Hose7, Bruno Paiva8, Minh Diem Vu9.
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.Entities:
Keywords: BCMA; T cell bispecific antibody; immunotherapy; multiple myeloma; redirected cell killing
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Year: 2017 PMID： 28262554 DOI： 10.1016/j.ccell.2017.02.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743