Homogeneous assay for monoclonal antibody detection in serum

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DESCRIPTION (provided by applicant): The long term goal of this application is to develop a device to provide rapid point of care analysis of the state of antibodies drugs within patient serum. Antibodies are widely used in a variety of applications, as therapeutic agents and reagents in biological assays. The ability to detect and quantify antibodies is a key aspect in many of their applications. Detection of antibodies and other protein therapeutics in a biological sample is critical in medical applications requiring determination of diagnostic and/or prognostic factors. However, determining the pharmacokinetics of a particular antibody can be problematic, especially when the detection is performed against a high background, as in a biological sample. There are two key applications. (1) Dosing schedules and routes of administration for antibody drugs are developed with many uncertainties and are often refined through pre-clinical and clinical studies where the need for simple and reliable pharmacokinetic assays is acute. The specific biology of a given antibody target can also lead to additional complications from the conventional dose escalation paradigm. (2) Antibody cancer drugs would be more economical and safer if the dose for each patient could be adjusted based on the antibody levels detected in the serum of the patient after each injection since the great variability in patient metabolism and tumor load is not captured in traditional dosage schemes. An enhanced detection system has been developed that can rapidly determine the concentration of antibody drugs present from blood samples. This research will focus on the development of this technology to further improve the assay in terms of reliability and sensitivity. Alemtuzumab (anti-CD52) will be used as a development model for assay refinement. It is currently used commonly in patients with chronic lymphocytic leukemia (CLL). The research will consist of three phases. 1) Development of a first order homogeneous assay for measurement of antibody. 2) Development of a novel enhancement technique for high sensitivity detection. 3) Determination and implementation of an assay kit to allow for point of care detection and analysis.