Antibodies against the B cell-specific antigens CD20 and CD19 have markedly improved the treatment of B cell-derived lymphoma and autoimmune diseases by depleting malignant and autoreactive B cells. However, since CD20 and CD19 are also expressed on healthy B cells, such antibodies lack disease specificity. Here, we optimize a previously developed concept that uses bispecific antibodies to induce apoptosis selectively in malignant and autoreactive B cells that express the death receptor CD95. We describe the development and characterization of bispecific antibodies with CD95xCD20 and CD95xCD19 specificity in a new IgG-based format. We could show that especially the CD95xCD20 antibody mediated a strong induction of apoptosis in malignant B cells in vitro. In vivo, the antibody was clearly superior to the previously used Fabsc format with identical specificities. In addition, both IgGsc antibodies depleted activated B cells in vitro, leading to a significant reduction in antibody production and cytokine secretion. The killing of resting B cells and hepatocytes that lack CD95 and CD20/CD19, respectively, was marginal. Thus, our results imply that bispecific anti-CD95 antibodies in the IgGsc format are an attractive tool for a more selective and efficient depletion of malignant as well as autoreactive B cells.
The first concern of the war was to make a levy and call the veterans back to service. The strong communities were appointed for operating workshops for weapons; gold and silver was coined at Antioch, and all things were hastened, each in their proper place through the right officials.-Tacitus, Histories 2.82At the beginning of his bid for the Roman emperorship, the general Vespasian took stock of Syria and the allegiances pledged to him by both the people there and the ones in the surrounding provinces. 1 Berytus hosted a war council. Troops poured in from Judea. Client kings of the region offered their support. Antioch-minted coins. This was neither the first nor the last time that the mint or mints at Antioch would manufacture struck money for an outside conqueror. Indeed, from the earliest of the Seleucid kings to the Roman emperors of Late Antiquity, the operations within the city repeatedly put forth the coins of these ruling authorities. Some of the coins mimicked the designs of those produced elsewhere in the empire; others bore idiosyncratic symbols of Syria. When Antioch's mint(s) and workshop(s) were not consumed with manufacturing issues for these rulers, they created coins for the citizens themselves and celebrated values integral to this population. Whoever the authority, these coins passed through the hands of people within and outside the city. Some remained local to the city's urban space and hinterland, while others moved great distances in the purses of traders, travelers, soldiers, and officials. The wealth of evidence inherent to these objects both in their craft and movement makes them a valuable resource for reconstructing the history of Antioch over time and space.This book begins to synthesize the myriad of historical, political, cultural, geographical, and fiscal data contained within the minted coins of Antioch through the methodologies of Exploratory Data Analysis (EDA);
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