Development of a drug discovery method targeted to stromal tissue

Abstract

Several diseases are characterized by alterations in the molecular distribution of vascular structures, presenting the opportunity to use monoclonal antibodies for clinical therapies. This pharmaceutical strategy, often referred to as “vascular targeting”, has promise in promoting the discovery and development of selective biological drugs to regulate angiogenesis- related diseases such as cancer. Various experimental approaches have been utilized to discover accessible vascular markers of health and disease at the protein level. Our group has developed a new chemical proteomics technology to identify and quantify accessible vascular proteins in normal organs and at disease sites. Our developed methodology relies on the perfusion of animal models with suitable ester derivatives of biotin, which react with the primary amine groups of proteins as soon as the molecules are attached. This presentation reports biomedical applications based on vascular targeting strategies, as well as methodologies that have been used to discover new vascular targets. The identification of antigens located in the stromal tissue of pathological blood vessels may provide attractive targets for the development of antibody drugs. This method will also provide an efficient discovery target that could lead to the development of novel antibody drugs.