Abstract

Abstract Pierian Biosciences has developed the ChemoINTEL platform for high-throughput, semi-automated quantification of cellular responses to chemotherapeutics. ChemoINTEL relies on a microscopy-based process that captures and analyzes single cell behavior to reflect responses within a population. The platform is customizable to a variety of small molecule panels, either specific to certain tumor types or for titration screening of small molecules in development. Automated imaging of each well of a 384-well plate over time provides real-time kinetic response data under a variety of treatment conditions. Brightfield and fluorescent images are used to determine quantitative changes in morphology and molecular metrics reflecting induced apoptosis and cell death. Unique to ChemoINTEL as a drug screening platform is the quantification of intensity values, at the single cell level versus whole well fluorescence, for each fluorescent probe at each timepoint through a high-throughput analysis routine. These data are further processed through an internally developed algorithm to compare a treated population’s response relative to an untreated control and reports a sensitivity score. By combining different treatment conditions, the platform provides intelligent design of single agent or combination treatment approaches. By analyzing individual cells in the population, ChemoINTEL aids in better understanding response of tumor cell sub-populations to different chemotherapeutic agents. As a compound library screening tool or potential clinical diagnostic, Pierian Biosciences’ quality-controlled processes ensure all its equipment, reagents and processes follow ISO17025 guidelines to ensure the quality of all data generated. Each assay is internally controlled to include a standard cell line, whose response is monitored for accuracy of the reported results. In collaboration with several biorepositories and through the development of a standardized dissociation approach resulting in purification of viable primary tumor cells, the ChemoINTEL platform is also under development to assess chemotherapeutic response within patient populations. In conjunction with the ChemoINTEL platform, Pierian Biosciences has also developed a sophisticated multi-color flow cytometry platform (ImmunoINTEL) that when used in conjunction with ChemoINTEL provides information on the purity of isolated primary tumor cells prior to plating, as well as information on the cell populations present within the tumor microenvironment. These two platforms can be further complexed to evaluate immunotherapies in combination with front-line therapies. In summary, Pierian Biosciences has developed a high-throughput, multi-parametric platform for both drug development and diagnostic applications. Note: This abstract was not presented at the meeting. Citation Format: Kellye C. Kirkbride, Kevin J. Polach, Samantha J. Braxton, Megan D. Hoeksema, Dustin C. Rogers, Patricia Ladd-Ward, Durdica Vojnic Zelic, Santosh Putta, Matt Westfall, Norman Purvis. ChemoINTEL: A high-throughput, multi-parametric compound screening platform for intelligent lead compound and therapeutic combination identification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 294.

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