Transarterial Chemoembolization Combined with Immune Checkpoint Blockade in an Animal Model of Hepatocellular Carcinoma

Liver cancer claims many lives worldwide. Developed countries have suffered an 80% increase in occurrence over the last 15 years. Patients with intermediate stage disease do not have as many options for treatment as those with beginning stage disease ( surgery, transplant,chemotherapy and radiation). Intermediate stage patients typically survive only 15-47 months. This study will attempt to find a treatment that will improve those outcomes. We will combine the delivery of chemotherapy drugs attached to tiny glass beads directly to liver tumors (traditional therapy) with immunotherapy (the treatment of disease with substances that stimulate the body's natural immune response) in a rat model of liver cancer. This is a fairly new and exciting immunotherapy treatment called Immune Checkpoint Blockade. We will use a molecule called PD-1 which can restore the immune system's ability to fight tumor cells. We expect this strategy of combining radiation with immunotherapy will enhance the ability of both treatments. We will also investigate the use of anti-tumor drugs and their effect on rat liver tumors which will allow us to identify potential immune system changes following treatment that we may be able to combine with the above PD-1 therapies. This may allow us to identify the preferred class of drugs for stimulating the immune system response to liver tumors.