Abstract 58: High throughput 3D tumor model drug screening technology

Abstract

Abstract Two-dimensional (2D) cancer cell cultures, or monolayers, remain the standard for testing cancer drugs prior to animal studies due to their simplicity and compatibility with standard plates and commercially available robotic tools. However, monolayer cell assays often fail to predict the efficacy of cancer drug candidates resulting in 80% of cancer drugs failing in animal drug studies and contributing to the extremely high costs of cancer drug discovery. Unlike solid tumors, the standard 2D cell cultures allow cancer cells unrestricted access to nutrients and oxygen and lack intercellular communications that result in inaccurate drug efficacy data. Three-dimensional (3D) tumor models are biologically relevant cell cultures that reproduce key properties such as diffusion limitations and cellular network of solid tumors that influence cancer drug efficacy. To promote the use of 3D cancer cell cultures in oncology drug discovery, OncoSolutions has engineered a novel technology to generate biologically relevant 3D tumor models that uniquely meets the needs of the pharmaceutical industry. OncoSolutions’ technology is highly robust and reliable for drug screening and available in high throughput format (1536 microplate) to accommodate the large drug libraries of the pharmaceutical industry. Importantly, the technology utilizes standard microplates that are compatible with commercially available automated liquid handling and analysis tools to reduce associated costs and increase speed for formation and analyses. OncoSolutions’ groundbreaking 3D culture technology is based on the immiscibility of highly aqueous solutions of polyethylene glycol (PEG) and dextran (DEX) to form a stable two-phase system. Cancer cells are mixed with the denser aqueous DEX phase solution and robotically dispensed as a nanodrop into a well of a standard microwell plate containing the immersion aqueous PEG phase. Cells remain entrapped in the nanodrop to autonomously form a single, compact 3D culture per well of the microplate within 24 hours. Unlike existing techniques, our technology quickly and reliably forms highly reproducible 3D cancer cell cultures with a standard deviation of less than 10% of the average 3D culture diameter within microplates. OncoSolutions’ technology has been used for biologically relevant standard chemotherapeutic testing and displayed superior robustness through Z-factor measurement (a statistical robustness measurement). In addition to evaluating the viability response of 3D cancer cell cultures generated with OncoSolutions’ technology, an assay for determining the apoptotic effects on 3D cancer cell cultures following drug treatment was optimized. Importantly, tumor models grown with OncoSolutions’ technology have provided more predictive models of animal drug responses than standard monolayer cultures and can reduce the time and costs associated with the high failure rate of cancer drugs in animal studies. Citation Format: Stephanie L. Ham, Emily Mulvany, Hossein Tavana. High throughput 3D tumor model drug screening technology [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 58.