03:09 PM Abstract No. 219 Local immunotherapy: Intra-arterial liver tumor vaccination in a pig model of metastatic pancreatic cancer

Abstract

Locoregional therapy lacks the ability to treat systemic disease. Systemic chemotherapy or immunotherapy has significant systemic side effects. Here, we present a proof-of-concept of intra-arterial immunotherapy using saponins (a vaccine adjuvant) in a pig tumor model. Liver and peripancreatic tumors were induced in an Oncopig (a transgenic pig with Cre-inducible p53 and Kras mutations) using an adenoviral vector carrying the Cre recombinase gene. A lipiodol/saponin emulsion was injected selectively into a branch of the hepatic artery through a 4 F catheter. Response to therapy was evaluated on contrast-enhanced CT and necropsy. As a negative control, selective hepatic artery embolization using 100-300 micron Embospheres was performed in a different pig. After selective hepatic artery immunoembolization using the lipiodol/saponin emulsion, CT performed 3 days later showed 19% decrease in size of the embolized liver tumors (n=2), 71% decrease in size of an unembolized liver tumor (n=1), and 25% decrease in size of peripancreatic tumors (n=2). On histology, tumor-infiltrating lymphocytes were seen in the necrotic liver tumors, and no viable tumor cells were seen in the liver or peripancreatic tumors. In the negative control pig (n=1), selective hepatic artery embolization using Embospheres resulted in tissue necrosis without a detectable local immune response on histology. In a pig model, intra-arterial tumor vaccination using lipiodol/saponin emulsion resulted in tumor-infiltrating lymphocytes, tumor necrosis, and regression of both intrahepatic and extrahepatic tumors. Additional experiments are necessary to confirm these encouraging preliminary results.