This Small Business Innovative Research Phase I project describes innovative yeast- and phage-based technologies to rapidly and accurately produce high quality, reliable, and inexpensive monospecific antibody molecules for use in cancer research. These reagents will be used in antibody microarray biochips to interrogate network of proteins involved in signaling pathways associated with cancer and autoimmune diseases. The ErbB receptor tyrosine kinase (RTK) family of receptors is one family whose over-expression and over-activation is associated with cancer and autoimmune diseases. This family of receptors (ErbB1, ErbB2, ErbB3, and ErbB4) has been the target of multiple drug development strategies. However, there is a serious shortage of high quality and reliable antibody reagents used to identify and characterize molecular pathways associated with this family of physiologically important receptors. Here, yeast- and phage-based expression systems will be used to generate and validate pairs of monospecific antibodies. These antibody pairs would be able to distinguish active states of these receptors. The utility of these antibodies will then be examined in a high throughput microarray system. This technology may also be applied more broadly in developing pairs of antibodies specific for other disease-relevant proteins that could be used to understand the associated signaling networks. Ultimately, this knowledge will enable the creation of effective therapeutics. These pairs of antibodies will be used in the Company's internal drug development efforts as well as commercialized for use by other academic and industrial entities. POTENTIAL COMMERCIAL APPLICATIONS Despite the high level of interest in the role of ErbB receptors in disease, there is a shortage of high quality and reliable antibodies that are specific for these receptors. The validated pairs of antibodies developed here will address this shortage and have high commercialization potential. Currently available antibodies are limited in their quality and utility for use in protein microarrays. Antibodies produced here will be developed specifically for use in protein microarrays and thus address the shortcomings of existing reagents. Consequently, the antibodies generated here can be commercialized individually, or as part of a complete platform. Furthermore, this technology may be used in generating and commercializing antibody reagents for the study of other cellular signaling networks for which there is a limited reagent pool. These antibody reagents will also be of great interest to pharmaceutical companies that are already engaged in ErbB-based therapeutics development, because of the role of this family of receptors in multiple diseases.
