Development of an Immunodeficient Pig Model for Pancreatic Cancer Xenotransplantation Using Splenectomy, Thymectomy, and Oral Immunosuppression

<i>Background and Objectives</i>: Animal models are widely used in medical research, but most are limited to small or medium-sized species due to logistical constraints. However, pancreatic cancer research and surgical xenograft models require large animals with anatomical similarities to humans and minimal immune rejection. This study evaluates the feasibility of an operative immunodeficient pig model for patient-derived xenografts. <i>Materials and Methods</i>: During the period of October 2020 and October 2021, four pigs were used to establish a pig model at Seoul National University Bundang Hospital. A conventional pig 40 weeks of age was used. After introduction into the animal laboratory, splenectomy and thymectomy were performed to minimize B-cell and T-cell function. One week after the initial operation, oral immunosuppression was administered. After 4 weeks, human PDAC cells were implanted in the liver and pancreas. After 4 weeks of implant, the pigs were sacrificed, and the operative and pathologic findings were analyzed. <i>Results</i>: All four pigs survived the 9-week experiment. Indwelling venous catheters for drug-level monitoring were attempted but failed. Splenectomy and thymectomy were deemed to be feasible and effective. Oral immunosuppression was acceptable, but the initial dosage was better tolerated at low levels. Out of the four pigs, one pig showed a mass formation at the cell line injection site, demonstrating reactive cell clusters on pathology. <i>Conclusions</i>: This pig model using conventional pigs is a feasible model of immunosuppression. It is necessary to fine-tune the oral immunosuppression dosage and develop methods for the frequent monitoring of immunosuppression levels.