Challenge to the development of molecular targeted therapy against a novel target candidate identified by antibody proteomics technology

Abstract

Disease proteomics that systemically analyzes and identifies differentially expressed proteins between healthy and diseased samples is a potentially useful approach for obtaining target proteins for drug development. To date, however, very few target proteins have been identified from this field. A key issue that remains to be resolved is how to correctly identify target proteins from a number of potential candidates. To circumvent this problem, we have developed ''antibody proteomics technology'' in which a single chain Fv phage antibody library is utilized for proteome analysis. Here, we describe the application of this technology by primarily focusing on Eph receptor A10 (EphA10), a novel breast can- cer-related protein that is a promising target for antibody drugs. To establish an effective and safe targeted cancer ther- apy, it is important that the target is specifically expressed in cancer tissues. Therefore, we attempted to analyze the EphA10 expression profiles. Tissue microarray analysis showed that EphA10 was expressed in all subtypes of breast can- cer containing triple negative breast cancer cases. On the other hand, EphA10 was only expressed in testis tissue among 36 kinds of normal tissues. Thus, EphA10 could be a highly cancer-specific protein, making it a promising target for female breast cancer patients. Finally, we examined the anti-tumor effect by anti-EphA10 antibody, aiming for the de- velopment of a novel EphA10 targeting therapy. Administration of the antibody showed that tumor volumes were signifcantly inhibited. Our results suggest that targeting EphA10 in breast cancer cases might be a promising new form of therapy.