TECHNOLOGY FOR DRUG DISCOVERY AND CANCER PATIENT TESTING

最近，一项新的细胞生物学技术（称为反应动力学，或KOR）被一名申请者发明并在白血病细胞上进行了验证。该技术可以自动实时监测化学和生物制剂诱导细胞凋亡的效果，并对培养的活细胞进行高通量筛选。此外，该方法可以在同一实验培养中，很好地鉴别和定量增殖、细胞抑制；坏死和细胞凋亡。虽然这项新技术还处于起步阶段，但它已经揭示了迄今为止未被认识的药物暴露时间、剂量、细胞活力、增殖或凋亡之间的关系，并产生了各种细胞类型暴露于化疗药物或生物制剂的特征性反应模式。简而言之，从该技术衍生的生物测定提供了连续监测光密度的细微变化，特别是当细胞群体暴露于各种刺激或抑制剂时的侧光散射特性。这表明，这种自动化的体外测量可能为药物发现提供一种新的方法，预测药物在体内的功效，并提供更多关于药物作用机制的信息，而不是任何其他细胞反应测定。这项创新技术及其相关的新概念和医学信息学软件将包括在目前正在申请的使用、技术和软件专利中。我们的研究表明，为了获得药物诱导细胞凋亡的准确图像，必须在细胞最大凋亡时进行检测。由于该时间随药物、剂量和细胞类型的不同而变化，因此动力学（而不是终点）分析是确定最大凋亡时间的唯一方法。与所有其他现有的细胞凋亡测定方法形成鲜明对比的是，自动KOR测定方法简单、廉价，并且在整个药物暴露期间提供细胞培养物的实时、连续和动态监测。这种KOR检测已经在白血病细胞中得到验证，我们的I期目标是测试将这种检测扩展到乳腺癌和其他实体肿瘤的可行性。拟议的商业应用：自动化的新细胞生物学技术将作为一种新方法上市：1)高通量筛选细胞用于新药先导；2)化疗患者的化疗敏感性和耐药性预测试；3)细胞凋亡和细胞生物学相关领域的学术研究；4)医学信息学软件协助临床决策

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