A single injection of the 102-year-old tuberculosis vaccine, BCG, has proven effective at triggering an immune response in mice and shrank their liver cancer tumors, according to research by UC Davis Health. The findings suggest that BCG might be an alternative way of treating this notoriously hard-to-treat cancer.
As the most common type of liver cancer, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Despite treatment options that include surgery, radio- and chemotherapy, immunotherapy and liver transplant, outcomes remain bleak.
In the search for an alternative treatment for HCC, researchers from UC Davis Health undertook a study to see whether the century-old Bacillus Calmette-Guérin (BCG) vaccine, used to protect against tuberculosis, was an effective anti-cancer agent.
Studies have found that in addition to its specific effects against TB, BCG has non-specific protective effects, including immune system effects, with systemic implications. The US FDA has already approved it for the treatment of bladder cancer, and clinical trials have explored its use in fibromyalgia and diabetes. So, the researchers were keen to test its effect on this stubborn form of liver cancer.
“HCC is very difficult to treat,” said Yu-Jui Yvonne Wan, the study’s corresponding author. “This cancer is considered a cold tumor, which does not respond well to immunotherapy. We had a good reason to believe that the BCG vaccine could stimulate an immune response. So, we gave a dose of BCG to mice with liver cancer, and to our surprise, it was enough to activate the body’s immune system and reduce tumor load.”
The researchers administered a single dose of BCG under the skin, the same way it’s given to humans, to mouse models of liver cancer. They found the treatment reduced inflammation and promoted the infiltration of immune cells, particularly cancer-fighting T cells and macrophages, into liver tumors, shrinking them. BCG also triggered the IFN-gamma signaling pathway, which facilitates tumor cell recognition and elimination through the recruitment of T cells.
“We discovered that the BCG treatment resulted in the movement of T cells and macrophages to the tumor,” Wan said. “It also activated the body’s immunity and enhanced IFN-gamma signaling, which contributes to an anti-HCC effect.”
Other research has shown that BCG’s effects on immunity affect the sexes differently, but the same was not seen in the current study.
“While previous studies have shown sex differences in BCG effects on immunity, our data showed that both male and female HCC mice responded to the BCG treatment,” said Wan.
The researchers plan to investigate whether whether BCG can be used as a preventive for liver cancer and whether it’s effective in treating other types of cancer.
“If BCG treated a tough tumor like liver cancer, I’m optimistic it can work well on other hard-to-treat cancers,” Wan said. “We would need more research to move onto the next step. For example, we don’t know how long this immune memory lasts, so [the] efficacy of this vaccine over time is still a mystery. The mechanism [of action] can be complicated, and further research is needed.”
The study was published in the journal Advanced Science.
Source: UC Davis Health