TECHNOLOGY FOR DRUG DISCOVERY AND CANCER PATIENT TESTING

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A new cell biology technology, (called Kinetics Of Response, or KOR) was recently invented and validated on leukemia cells by one of the applicants. The technology- allows automated, real-time monitoring of the apoptosis-inducing effects of chemical and biological agents and makes feasible high throughput screening on live cells in culture. In addition, the assay can, m the same experimental culture well, discriminate and quantify proliferation, cytostasis; necrosis and apoptosis. Though still in its infancy, this new technology has already revealed heretofore unrecognized relationships between the drug exposure time, dose, cell viability, proliferation or apoptosis and generated characteristic response patterns of various cell types exposed chemotherapeutic drugs or biological agents. In brief, the bioassays derived from this technology provide continuous monitoring of subtle changes in optical density, in particular the side light scattering properties of cell population when they are exposed to various stimulatory or inhibitory agents. It is suggested that such automated in vitro measurements may allow a new approach to drug discovery, predictions of the in vivo efficacy of drug and more information about the drug's mechanism of action than is feasible with any other cell response assays. This innovative technology, its associated new concepts and medical informatics software will be covered under use, technology and software patents which are currently pending. Our studies suggest that in order to obtain an accurate picture of drug induced apoptosis one must assay at the time of maximal apoptosis. Since that time varies with drug, dose and cell type, a kinetic (as opposed to an endpoint) analysis the only, way to identify the time of maximum apoptosis. In sharp contrast, to all other existing apoptosis assays, the automated KOR assays are simple, inexpensive and provide live, continuous and kinetic monitoring of cell cultures during the entire period of drug exposure. This KOR assays have been validated for leukemia cells and our phase I objective is to test the feasibility of extending this assay to breast cancer and other solid tumors. PROPOSED COMMERCIAL APPLICATION: The automated new cell biology technology will be marketed as a new approach to: l) High throughput screening on cells for new drug leads 2) Chemosensitivity and Resistance pre-testing in patients contemplating chemotherapy 3) Academic research in apoptosis and related areas of cell biology 4) Medical informatics software to assist with clinical decisions