Models of EBV Cancer

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CORE C – PROJECT SUMMARY The Preclinical Models of Epstein-Barr Virus (EBV) Cancer Core provides major resources to the three Program Project Investigators, including viral mutants and strains, EBV+ and EBV- nasopharyngeal carcinoma and gastric carcinoma cell lines; human gastric cancer organoid cultures; patient derived xenografts and other in vivo models of EBV-associated cancers; compound testing; and recombinant viruses. Core C has acquired a large repository of EBV+ and EBV- epithelial (gastric and nasopharyngeal) and lymphoid cell lines that have been fingerprinted and are routinely verified by microsatellite/short terminal repeat (STR) testing to exclude cross- contamination. In collaboration with Dr. Calvin Kuo (Stanford University), gastric cancer organoid cultures that are now continuously available through Core C at The Wistar Institute. Organoids are superior to standard cell culture because they recapitulate many features of the organs that they are derived from, including organ ultrastructure, and mimic the tumor microenvironment. These organoid cultures will provide important tools for studying viral and cellular determinants of Epstein-Barr virus-associated cancers (Project 1) and for drug screening (Projects 2 and 3). Importantly, these organoid cultures are genetically tractable and TP53 and ARID1A knockout organoid cultures are already available in Core C. In addition to cell culture models, Core C routinely performs studies using several murine models of EBV- associated cancers. Patient-derived xenografts that are exclusively maintained in vivo are available for all three Projects. Cell line-derived models of EBV associated gastric carcinoma and NPC have been adapted for bioluminescent imaging studies. These murine models will be used for compound testing (Projects 1-3) in collaboration with Core B. Finally, Core C will provide high-titer, recombinant EBV (Projects 1-3) using a bacterial artificial chromosome system to interrogate the specific contributions of EBV genes to the development of cancer.