A single injection of the 102-year-old tuberculosis vaccine BCG has been shown to be effective in triggering an immune response and shrinking liver cancer tumors in mice, according to research from UC Davis Health. The findings suggest BCG may be an alternative treatment for this notoriously difficult-to-treat cancer.
As the most common type of liver cancer, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Although treatment methods include surgery, radiotherapy and chemotherapy, immunotherapy and liver transplantation, the efficacy is still not optimistic.
In the search for alternative treatments for HCC, researchers at UC Davis Medical Center conducted a study to explore whether the century-old Bacillus Calmette-Guérin (BCG) vaccine, used to prevent tuberculosis, is an effective anti-cancer drug.
Studies have found that in addition to its specific effect on tuberculosis, the BCG vaccine also has non-specific protective effects, including effects on the immune system, with systemic effects. The U.S. Food and Drug Administration has approved BCG for the treatment of bladder cancer, and clinical trials have explored its use in fibromyalgia and diabetes. So researchers are keen to test its efficacy against this stubborn form of liver cancer.
Yu-Jui Yvonne Wan, the corresponding author of the study, said: "HCC is very difficult to treat. This cancer is considered a cold tumor and does not respond well to immunotherapy. We have good reason to believe that BCG can stimulate an immune response. Therefore, we injected a certain dose of BCG into mice with liver cancer, and to our surprise, BCG was enough to activate the body's immune system and reduce the tumor load."
The researchers administered a single dose of BCG subcutaneously in a mouse model of liver cancer, the same way BCG is given to humans. They found that this therapy reduced inflammation and promoted the infiltration of immune cells, especially anti-cancer T cells and macrophages, into liver tumors, thereby shrinking the tumors. BCG vaccine can also trigger the IFN-gamma signaling pathway to promote the recognition and elimination of tumor cells by recruiting T cells.
"We found that BCG treatment caused T cells and macrophages to move toward the tumor," Wan said. "It also activates the body's immunity and enhances IFN-gamma signaling, thereby playing an anti-HCC role. Although previous studies have shown sex differences in the impact of BCG on immunity, our data show that both male and female HCC mice respond to BCG treatment."
Other studies have shown that BCG's effects on immunity affect the sexes differently, but the same was not found in the current study.
The researchers plan to investigate whether BCG can be used to prevent liver cancer and whether it can be effective in treating other types of cancer.
"If BCG can treat stubborn tumors like liver cancer, I believe it will also be very effective in other hard-to-treat cancers," Wan said. "We need more research before we can move to the next step. For example, we don't know how long this immune memory will last, so the long-term efficacy of this vaccine remains a mystery. The mechanism of action may be complex and requires further study." "
The research was published in the journal Advanced Science.