Activated TCISMs (Red and Green staining) in Human Psoriasis Tissue (Courtesy of Dr. Mayumi Fujita, Department of Dermatology University of Colorado Denver)

By focusing on activated macrophages, a key white blood cell in the adaptive immune system, Western States is designing drugs that target the pathogenesis of autoimmune disease while avoiding suppression of the innate immune system. The goal of WSBI’s drug discovery and development research programs is to identify human CD4+ T cell and macrophage proteins that mediate adaptive immunity but leave the innate immune system intact.

WSBI refers to these novel human T cell proteins as “T cell Cytokine–Inducing Surface molecules”, or TCISMs®. With the exception of a few TNFα family members, the identification of other human T cell proteins that mediate early adaptive immune processes for the production of proinflammatory cytokines is completely unknown at this time.

Western States has recently shown that two important human TCISMs are upregulated upon CD4+ T cell activation and physiologically associate at the T cell membrane surface. T cell-driven macrophage-cytokine levels were decreased by 90-100% when expression was simultaneously inhibited by dual siRNA knockdown for both T cell proteins.

WSBI is currently designing and preparing a panel of mammalian-cell derived, novel and proprietary, biphasic, high-affinity antibodies to these targets to act as selective and specific cytokine antagonists for rheumatic diseases.