Preclinical evaluation of the CD38-targeting engineered toxin body MT-0169 against multiple myeloma.

Despite significant progress in the treatment of multiple myeloma (MM), relapsed/refractory patients urgently require more effective therapies. We here describe the discovery, mechanism of action, and preclinical anti-MM activity of engineered toxin body MT-0169, a next-generation immunotoxin comprising a CD38-specific antibody fragment linked to a de-immunized Shiga-like toxin A subunit (SLTA) payload. We show that specific binding of MT-0169 to CD38 on MM cell lines triggers rapid internalization of SLTA, causing cell death via irreversible ribosome inhibition, protein synthesis blockade, and caspase 3/7 activation.

Factors associated with work ability among employees of an Italian university hospital.

Background: A growing body of evidence clearly documents the benefits of integrated systems approaches to protecting and promoting the safety, health and well-being of workers. The purpose of this study is to provide a holistic view of the work ability of employees of an Italian University Hospital measuring their resources in relation to job demands. In particular, it examines socio-demographics, family and organizational antecedents of health professionals' work ability.

Domain mapping of the human cytomegalovirus IE1-72 and cellular p107 protein-protein interaction and the possible functional consequences.

Our previous work demonstrated that following human cytomegalovirus (HCMV) infection of fibroblasts, there was a protein-protein interaction between the HCMV IE1-72 immediate-early (IE) protein and the cellular p107 protein which resulted in the alleviation of p107-mediated transcriptional repression of E2F-responsive promoters. In a further characterization of this interaction, we now show that IE1-72 binds to the N-terminal portion of p107, not the C-terminal 'pocket' region that binds E2F-4, and where a number of other viral gene products bind. Additionally, we show that exons 2 and 3 of IE1-72 are required for binding to p107.