MD Anderson Cancer Center MD Anderson Cancer Center Houston, Texas, United States
Background: Existing large animal models for cancer suffer from significant limitations. RWabbit and woodchuck models present numerous challenges. Swine models have a closer match to human physiology and scale, yet tumor models are extremely uncommon.
Purpose/Objective: The Oncopig is an immunocompetent, transgenic model but real-world experience beyond the originating lab is sparse. It uses a transgene with 2 mutations found in many cancers, KRAS and TP53. When activated by Cre recombinase, KRAS is expressed, and p53 is eliminated. We report initial experience with the model and provide context with the existing alternatives.
Materials & Methods: Under an approved protocol with general anesthesia, 9 Oncopigs in 3 cohorts were inoculated in the liver with an adenoviral vector up to 4 times in each liver, in separate lobes for a planned total of 36 tumors. An 18G biopsy was obtained and incubated for 20-30 minutes at ambient temperature in vector solution. Cores were then reintroduced into the biopsy site in gelfoam slurry. Animals were recovered and imaged weekly by CT scan without and with contrast, with euthanasia at 2, 3, or 4 weeks post-inoculation. After sacrifice, necropsy was performed and specimens collected for fixation and immunohistochemistry.
Results: All animals survived as planned. By CT imaging with contrast, rim-enhancing tumors of up to approximately 3 cm in size were induced in nearly all sites inoculated. An exudative growth between liver and diaphragm was noted in several pigs. Histologically, these tumors were found to contain primarily inflammatory cells but scant evidence of carcinoma.
Conclusion: Early experience in our hands suggests that tumors were obtained, but utility will depend to a great extent on intended use. Caution is warranted and further studies must be done to define the conditions in which a true carcinoma is engendered.
