Abstract 1456: First successful engraftment of human liver cancer cell line in highly robust immunocompromised porcine model to test the tumor ablation efficacy by histotripsy

Abstract Liver tumor, commonly called Hepatocellular carcinoma(HCC), is the most common type of primary liver malignancy. It is the fourth leading cause of cancer-related deaths. Late diagnosis, location of the tumor, tumor burden, and metastases makes liver tumor very challenging to treat by liver transplantation, surgical procedures, and other ablation techniques like cryoablation and thermal ablation. Also, the absence of a preclinical animal model makes it challenging to develop and explore the feasibility of treatment modalities. Histotripsy is a non-invasive, non-ionizing, non-thermal, image-guided focused ultrasound ablation treatment method that uses high-pressure pulses to create acoustic cavitation, a “bubble cloud,” at the target. The bubble cloud expands and collapses, which ablates the tissue into an acellular homogenate. Pigs are ideal animal models as they closely resemble human anatomy and are significant in improving the translation to human patients. This study aimed to establish the feasibility of successfully ablating liver tumors by histotripsy using an immunocompromised porcine model to generate HepG2 human liver cancer cell line tumors in the liver of the immunocompromised pigs. The orthotopic porcine model was established using RAG2/IL2RG double knockout immunocompromised pigs. HepG2 cells were injected orthotopically into the liver of immunocompromised pigs. Three weeks after the injections, CT images and necropsy indicated successful engraftment and growth of liver tumors in the pigs. The ultrasound images and post-histotripsy treatment histology images showed confirmed ablation zones in the liver. Therefore, in conclusion, our preliminary results in the study could demonstrate, for the first time, a highly robust model of human liver cancer in a large animal model. Soon, we plan to conduct more such studies and explore all the possible utilities of these immunocompromised porcine models to develop therapeutic strategies to increase the efficacy of liver tumor ablation by histotripsy. Citation Format: Tamalika Paul, Khan M. Imran, Jessica Gannon, Brie Trusiano, Kristin Eden, Hannah Ivester, Madeline Mott, Manali Powar, Michael Edwards, Christopher Byron, Sherrie Clark-Deener, Kiho Lee, Eli Vlaisavljevich, Irving Coy Allen. First successful engraftment of human liver cancer cell line in highly robust immunocompromised porcine model to test the tumor ablation efficacy by histotripsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1456.