TMOD-39. A NOVEL EX VIVO TUMOR SLICE CULTURE SYSTEM AS A TOOL FOR BASIC AND CLINICAL RESEARCH

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Many cytotoxic and targeted therapies show promising activity in cultured cells but most fail to show equivalent efficacy in patients, indicating that the predictive power of cell culture models is limited. While patient derived xenograft (PDX) models are more faithful models of human cancer, they are very expensive and time consuming to generate and maintain, rendering them impractical models for most studies. To bridge the gap between in vitro cell culture and in vivo animal models, we developed a tumor slice culture system from PDX models and patient tumors. While other studies have described the use of tumor tissue slices cultures, our technology has multiple significant advantages. First, we developed a robust method to monitor real-time, longitudinal therapy response from each tumor slice over a 2-3-week period. This is in contrast to previous studies, which averaged sample responses at a single end point, usually 2-4 days in culture. Second, we adapted our technology to perform a medium-throughput drug screen. Our initial proof-of-principle study was performed with 119 FDA-approved oncology drugs on a colorectal PDX. We identified seven drugs that reproducibly suppressed tumor slice viability by >50% and we validated in vivo efficacy of one of the drugs. Third, we tested the robustness of our system by culturing multiple types of human cancer, including GBMs and medulloblastomas, indicating that our culture condition can be used to study brain tumors. In addition, we validated that our system can be used to culture fresh surgical discards from patient tumors for 12 days with intact histology and good viability. We propose that our tumor slice system is a powerful tool to understand the role of intra-tumoral heterogeneity, tumor microenvironment, therapy resistance, and the stem cell niche, and can be exploited to screen drug libraries to identify new drugs for brain cancer patients.

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