Treatment and Relapse Prevention of Hepatocellular Carcinoma by Combined Cryoablation-Immunotherapy
Abstract
Liver cancer is the second leading cause of cancer-related death, and the number of new cases rises each year. Veterans suffer from higher rates of liver cancer compared to the general United States population. Few patients are eligible for curative treatments such as surgery or a liver transplant. An alternative for some patients may be a minimally invasive treatment called “ablation,” where the tumor is destroyed using a special wand that is placed through a pinhole in the skin. Even with treatment, however, liver cancer can recur. There is a critical need to reduce recurrence after liver cancer treatments. We propose to improve ablation for liver cancer by stimulating the body’s own immune system to fight the cancer. This approach could dramatically improve the survival and quality of life for Veterans, active duty military, and others suffering from liver cancer. Immunotherapy is a strategy to treat disease by engaging the body’s defense system, the immune system. Immunotherapy can be used to treat liver cancer. In fact, the immune system successfully eliminates cancer cells all of the time. Cancers like liver cancer grow because they develop methods of avoiding or suppressing the immune response. Thus, strategies to help the immune system recognize the cancer and overcome this suppression could help it to make specialized immune cells that kill the liver cancer cells. These cells may live for many years to protect the body against the body against recurrences. Vaccines work by giving the body little pieces of a specific disease in order to teach the immune system to recognize the disease as foreign and respond by making specialized immune cells to fight it. A vaccine would be an excellent approach to stimulate the immune system to recognize and destroy liver cancer cells. However, there is a great deal of variability in liver cancers, and it would be prohibitive to make so many vaccines containing little pieces of all of the different liver cancers. An alternative, personalized approach is to use ablation to generate tumor debris while destroying the tumor then to stimulate the immune system to recognize the debris and mount an attack. We propose a variation of the vaccine strategy that combines ablation with a novel, nanotechnology developed from a plant virus called the cowpea mosaic virus (CPMV), which can safely stimulate the immune system of humans. “Cryoablation” is a form of ablation that uses ice to destroy tumors. Cryoablation leaves behind abundant tumor debris and stimulates inflammation, but the immune system is suppressed and does not recognize the tumor. In order to stimulate the immune system, we propose injecting CPMV into the tumor; this plant virus is safe to use because it does not infect humans. CPMV acts as a flare inside the tumor, stimulating the immune response to recognize and fight the tumor. Once activated, the immune system makes specialized immune cells that can patrol the body for tumor cells, even if they are at distant sites or if they appear in the future. Therefore, this combined treatment is designed to treat the liver tumor and any tumor cells that may have spread throughout the body while protecting against cancer recurrence. This novel treatment strategy offers a powerful cure, because it can eliminate the cancer throughout the body and over time. The immune response would be specific to the patient’s own cancer, which would maximize efficacy while minimizing any side effects associated with an activated immune system. Importantly, this combined approach could still be successful even if cryoablation fails to destroy the entire cancer. As such, cryoablation plus CPMV could be a treatment option for patients who cannot undergo other treatments because their cancer is too extensive or in a difficult location. This novel strategy is feasible and cost-effective, because it represents a simple variation of a minimally invasive procedure that is widely used in clinical pract
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010742
Entities
People
- Nicole F Steinmetz
Organizations
- United States Army
- University of California, San Diego