Single Chain Antibodies

About

Single chain antibodies directed to pancreatic β cells Overview: The intellectual property relates to β- or α-cell specific single chain antibodies (SCAs) that enable the specific and non-invasive transport of a selected therapeutic agent to pancreatic islet β- or α-cells. In one aspect, fusion proteins comprising a single chain antibodies (SCA) specific for pancreatic β- cells and a NEMO binding domain (NBD) [SCA B1-NBD fusion protein] protects islets against the deleterious effects of IL-1β in vitro, diabetogenic agents in vivo, and enables nearly complete protection from developing diabetes in multiple low dose streptozotocin (MLDS) treated mice. Taken together, the SCA B1-NBD chimera affords highly specific, targeted therapy to β-cells, and provides a novel, non-invasive strategy of SCA-mediated β-cell specific delivery with potential to prevent β-cell death. The need: Pharmacotherapy of type II diabetes aims to reverse insulin resistance, control intestinal glucose absorption, normalize hepatic glucose production, and improve beta-cell glucose sensing and insulin secretion. Because of the shortcomings of current treatments for diabetes, new modalities for type I and type II diabetes, as well as new diagnostic and prognostic methods are highly desirable. Evidence indicates that inadequate β-cell mass underlies type 1 and type 2 diabetes and that apoptosis or programmed cell death is the main form of β-cell death. Therefore, preserving β-cell mass presents a viable approach to disease management.