TB vaccine reduces liver cancer tumors in mice

BCG option for repurposing HCC treatment with Mechanistic insights

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A recent study by UC Davis Health discovered that giving mice with liver cancer a single dosage of the TB vaccine, Bacillus Calmette-Guérin (BCG), helped shrink their tumors and extend their lives. This is the first trial demonstrating the potential of the vaccination to treat liver cancer.

The BCG vaccine has been around for a hundred years and is made from live bacteria called Mycobacterium bovis. It’s widely used worldwide and considered safe.

BCG helps prevent tuberculosis and strengthens the body’s immune system. While the U.S. FDA already approved it for treating bladder cancer, its capability for treating other solid tumors like liver cancer wasn’t precise until now.

A recent study by Professor Yu-Jui Yvonne Wan found that just one shot of BCG under the skin can reduce liver scarring, improve liver function, decrease liver fat, and reduce tumors.

Wan, the study’s senior author and vice chair for research in the UC Davis Department of Pathology and Laboratory Medicine, said, “HCC is very difficult to treat. This cancer is considered a cold tumor, which does not respond well to immunotherapy. We had a good reason to believe the BCG vaccine could stimulate an immune response. So, we gave a dose of BCG to mice with liver cancer, and our surprise, it was enough to activate the body’s immune system and reduce tumor load.”

The researchers injected mice with liver cancer with BCG under the skin, just like how humans receive the BCG vaccine. They discovered that BCG decreased inflammation and boosted the activity of immune T cells. In particular, it enabled CD4+ and CD8+ T cells and M1 macrophages to enter the tumor.

Wan said, “We discovered that the BCG treatment resulted in T cells and macrophages moving to the tumor. It also activated the body’s immunity and enhanced IFN-γ signaling, contributing to an anti-HCC effect.”

Macrophages are the type of white blood cells that can fight cancer. BCG triggered IFN-γ signaling, leading to the death of cancer cells. The study also focuses on whether the impact of BCG on liver cancer depends on sex.

Wan explained, “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.”

Bacterial immunotherapy, like BCG, provides an alternative to current treatments using immune checkpoint inhibitors. It could transform how we treat HCC.

“Our research revealed that BCG immunotherapy for HCC is distinct and better than other options. It involves just one injection. In animal studies, BCG showed superior results in treating liver cancer compared to standard immunotherapies like anti-PD-1. This suggests a simpler treatment approach,” explained Wan.

The study suggests that the BCG vaccine could be repurposed to treat HCC. This is significant as BCG is already used safely worldwide.

Journal reference:

  1. Farzam Vaziri, Tahereh Setayesh et al., BCG as an Innovative Option for HCC Treatment: Repurposing and Mechanistic Insights. Advanced Science. DOI: 10.1002/advs.202308242.
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