A human icam-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo.

We isolated a tumor B-cell-targeting antibody, BI-505, from a highly diversified human phage-antibody library, using a pioneering "function-first" approach involving screening for (1) specificity for a tumor B cell surface receptor, (2) induction of tumor programmed cell death, and (3) enhanced in vivo antitumor activity compared to currently used treatments. BI-505 bound to intercellular adhesion molecule-1, identifying a previously unrecognized role for this receptor as a therapeutic target in cancer. The BI-505 epitope was strongly expressed on the surface of multiple myeloma cells from both newly diagnosed and relapsed patients. BI-505 had potent macrophage-dependent antimyeloma activity and conferred enhanced survival compared to currently used treatments in advanced experimental models of multiple myeloma

Characterization of rafts subtypes in monocytes of diabetic patients with and without neovascular complication

Purpose Diabetic retinopathy is a chronic inflammatory disease where the infiltration of plasma and neovascularization of the retina cause blindness. This disease affects millions of people in developed countries and early biological markers would better manage these patients. Methods For this purpose we purified monocytes, key players of inflammation, blood of healthy and sick people. On the surface of monocytes, there are dynamic structures called rafts membrane microdomains, which there are two subtypes: flat rafts and caveolae rafts. They correspond to dynamic assemblies and ordered cholesterol and sphingolipids. We isolated these rafts membranes of monocytes and studied protein AT2 (angiotensin receptor II) and gp91 (major membrane subunit of NADPH oxidase, producing enzyme superoxide anions), potential markers of the severity of diabetic retinopathy. Results Our results have shown a switch of cholesterol and sphingomyelin flat rafts to caveolae rafts. The analysis of the constituent proteins (flotillin and caveolin) and functional (AT2, gp91 and p47phox) have shown that these are mobile in the membrane in an inflammatory context. Subunits of NADPH oxidase seem to gather in caveolae rafts and more precisely when the enzyme is activated. Conclusion The proteins of interest and the switch composition of lipid rafts therefore would appear to be an indicator of the progression of diabetic retinopathy and it would be interesting to provide a mechanistic explanation for the evolution of this chronic vascular disease to consider potential therapeutic targets