Oncopigs: an inducible transgenic large animal cancer model to address pre-clinical assessments

Cancer research progress has been markedly hampered by the lack of clinically relevant systems in which to study the effects of mutational interactions on cancer phenotypes. To address this, we developed an inducible transgenic Oncopig®, a unique genotypically, anatomically, metabolically, and physiologically relevant large animal model that develops inducible site and cell specific tumors for preclinical study of human cancer. The Oncopig® harbors mutations found in >50% of human cancers- KRASG12D and TP53R167H- and results in tumors that recapitulate the phenotype and physiology of human cancers. As in human disease, TERT is solely expressed in Oncopig® cancer cells, and innate Oncopig® KRASG12D and TP53R167H driver mutations are heterozygous in nature. The Oncopig® size allows utilization of the same interventional tools, such as radiological, imaging and surgical devices all employed in human clinical practice. The Oncopig® is also an ideal model for investigation of drug toxicity, as its basal metabolic rate and xenosensor pregnane X receptor homology and functionality (responsible for the metabolism of half of all prescription drugs) are also very similar to humans. In addition, we have demonstrated the ability to genetically engineer Oncopig® cell lines to facilitate the controlled addition of gene mutations in induced tumors for improved preclinical investigation of the impact of cancer phenotypes on diagnostic and therapeutic approaches. Therefore, the Oncopig Cancer Model® fulfills current unmet clinical modeling, needs as the only FDA cleared large animal cancer model, that supports device, drug and diagnostic safety, risk and efficacy studies. (238 words)