Development of High Throughput Molecular Profiles for the Detection and Staging of Cancer

This Small Business Innovation Research Phase I project aims to develop a technology that employs polyclonal antibodies as a complex probe to discover tumor associated surface antigens, a process named Dual Immunostaining-mediated Subtractive Cloning(DISC). Antibodies have been the most powerful tools to dissect the expression and structure of proteins. Immune system has evolved to respond to foreign antigens by generating antibodies recognizing most, if not all, foreign epitopes. It is thus apowerful tool to search for structural and quantitative differences on cell surface proteins between a normal cell and a diseased cell. Disease-associated cell surface antigens are ideal markers for diagnostics and potential targets for therapeuticintervention. To discover novel disease-related cell surface molecules, we propose a novel technology that combines three proven techniques: whole cell immunization, flow cytometry and cDNA expression cloning, to identify surface antigens thatquantitatively or structurally unique to diseased cells such as cancer cells. These tumor-associated antigens identified in this process will be used to generate monoclonal antibody microarrays for the detection and staging of cancer in Phase II of theproject. DISC technology that Epitomics is attempting to develop in Phase I will lead to discovery of novel tumor associated antigens in a panel of human cancers (Phase II project). Rabbit monoclonal antibodies against these antigens will be producedfrom the cell lines generated in DISC process. Epitomics intends to develop and commercialize antibody microarrays for cancer detection and staging, using monoclonal antibodies for the existing and newly discovered tumor antigens.