Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment

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

Three-dimensional morphological analysis of intracranial aneurysms: a fully automated method for aneurysm sac isolation and quantification

Morphological descriptors are practical and essential biomarkers for diagnosis and/ntreatment selection for intracranial aneurysm management according to the current guidelines/nin use. Nevertheless, relatively little work has been dedicated to improve the three-dimensional/nquanti cation of aneurysmal morphology, automate the analysis, and hence reduce the inherent/nintra- and inter-observer variability of manual analysis. In this paper we propose a methodology/nfor the automated isolation and morphological quanti cation of saccular intracranial aneurysms/nbased on a 3D representation of the vascular anatomy.This work was partially supported within the CENIT-CDTEAM and CENIT cvREMOD projects funded by the Spanish Ministry of Innovation and Science-CDTI and partly within the framework of the @neurIST Project (IST-2005-027703), which is co- nanced by the European Commission within the IST Program of the Sixth Framework Programm