IGF::OT::IGF SBIR Topic 355: A 3D Perfusable Platform for HTS Across Diverse Racial/Ethnic Cancer Specimens To generate racially diverse patient-derived xenograft (PDX)-derived prostate cancer culture

Mimetas Us, Inc., Gaithersburg MD

Investigators

Abstract

African-American men have the highest incidence of prostate cancer (PCa) are more than twice as likely to die than Caucasian men in the US. Underlying factors that cause this disparity have yet to be confirmed in functional studies as representative in vitro models are not readily available to the research community. This problem has two origins. First, a diverse source of PCa tumor cells from representative racial and ethnic backgrounds does not currently exist. Second, the inaccuracy of two-dimensional (2D) cancer drug screening models in predicting in vivo tumor responses in patients is a major hurdle for effective candidate drug selection and contributes to the high rate of cancer drug clinical failures. This compounds the difficulty of assessing potentially subtle biological factors that may contribute to cancer health disparities (CHD). In this proposal, Mimetas and its collaborators at Rice University will develop and demonstrate the feasibility of a racially diverse population of PDX derived PCa cultures of Caucasian, Hispanic, and African-American origin in Mimetas 3D OncoPlate high-throughput platform containing 96 ex vivo micro tumors. Our platform will mimic the 3D tumor microenvironment by integrating co-cultured stromal cells, extracellular matrix (ECM), and continuous perfusion, to will better predict patient responses, and support CHD research. We will perform a drug screen of relevant therapeutics to display the reproducibility and predictive ability of our platform. In a potential Phase II, we will expand the number of culture models to a fully racially diverse set and develop outputs for metastatic and angiogenesis potential.