日本質量分析学会 第66回質量分析総合討論会

Program

Oral Sessions

Day 4, May 18(Fri.) 09:20-09:40 Room C (Seiun 2)

Target discovery method to stromal tissue for development of antibody drugs

(1NIBIOHN, 2Osaka Univ.)
oHaruhiko Kamada1, Tsuyoshi Inoue2

Monoclonal antibodies (mAbs) are increasingly being used in modern anticancer therapy either as intact immunoglobulins or as carriers for the selective delivery of bioactive molecules to the tumor site, thereby minimizing exposure to noninvolved organs. Several diseases are characterized by alterations in the molecular distribution of vascular structures, presenting the opportunity to use mAbs for clinical therapies. This pharmaceutical strategy, often referred to as “vascular targeting”, promises to promote the discovery and development of selective biological drugs to regulate angiogenesis-related diseases such as cancer. Our group has developed a chemical proteomics technology to identify and quantify accessible vascular proteins in normal organs and at sites of disease. The methodology relies on the perfusion of animal models with suitable ester derivatives of biotin, which reacts with the primary amine groups of proteins as soon as these molecules are attached. The biotin-labeled proteins can be efficiently recovered from normal and pathologic tissues by purification on streptavidin resins. The identification of antigens located in stromal tissue of pathological blood vessels may provide attractive targets for development of antibody drugs. This method will also provide an efficient target discovery that could lead to the development of novel superior antibody drugs.