Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment
Keywords: 
Materias Investigacion::Ciencias de la Salud::Hematología
Multiple myeloma
BCMA
Immunotherapy
T cell bispecific antibody
Redirected cell killing
Issue Date: 
2017
Publisher: 
Elsevier
OpenAIRE: 
info:eu-repo/grantAgreement/EC/ERC/680200MYELOMANEXT
ISSN: 
2211-1247
Note: 
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Citation: 
Seckinger, A. (Anja); Delgado, J.A. (Jose Antonio); Moser, S. (Samuel); et al. "Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment". Cell Reports. 31, 2017, 396 - 410
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.

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