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Home » 100-year-old BCG vaccine — promising treatment for liver cancer

100-year-old BCG vaccine — promising treatment for liver cancer


A while ago, I wrote about the 100-year-old BCG vaccine, for tuberculosis, which is being used to treat some forms of bladder cancer. A newly published study shows that it may be very effective in treating the most common form of liver cancer, which itself is the fifth most common cancer in the world. Liver cancer will affect about 41,630 Americans and cause about 29,840 deaths in 2024.

Any new treatment tool that can improve outcomes from this pernicious disease is important. This new research may give hope to those who have liver cancer.

As I usually do, I’ll take a look at this study and give you some highlights.

shallow focus photography of microscope bcg vaccine cancer
Photo by Chokniti Khongchum on Pexels.com

What is the BCG vaccine and how does it treat cancer?

The Bacillus Calmette-Guérin vaccine, or BCG vaccine, was initially developed to prevent tuberculosis. That disease is caused by a bacteria called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but they can also damage other parts of the body. Tuberculosis is treatable with advanced medicines, but it takes a long time and can be expensive. Without treatment, the patient will die.

The BCG vaccine works like most vaccines – it is made from an attenuated, live bovine tuberculosis bacillus, Mycobacterium bovis which induces an adaptive immune response against tuberculosis bacterium.

Tuberculosis (TB) is a leading cause of infectious disease deaths worldwide, second only to COVID. The vaccine’s development began in Lille, France in 1900, when Albert Calmette, an army physician, was working with Camille Guérin, a veterinarian, to understand how TB was transmitted.

Calmette and Guérin cultured TB bacteria on potato slices and found that after several passages of the microbes from one slice to a fresh one, they became less virulent over time. The researchers started to vaccinate calves with this live, weakened form of TB to protect cattle. By 1921, after over 200 generations of this weakened bacteria, the TB strain was stable and did not cause the disease in all animals they tested it on.

At the time of the vaccine’s development, French children born in a family in which someone had TB faced a 25 percent chance of dying from the disease within their first year of life. In 1921, Calmette and Guérin gave the first dose of BCG to a child born into a family with TB, and the child survived.

In 1924, a large clinical trial of more than 5,000 French children showed that the BCG vaccine had 93% effectiveness in preventing death in the first year of life. Based on the results of the clinical trial, France quickly adopted the vaccine, and soon thereafter, many more countries developed their version of the BCG vaccine and began mass vaccination of children.

As a result of the vaccine, tuberculosis was successfully eradicated in many countries, and the vaccine is rarely used in those countries. However, it is still given to about 100 million children every year in countries where tuberculosis is still endemic.

The BCG vaccine works like all vaccines in that it induces an adaptive immune response that “remembers” the pathogen, in this case, tuberculosis bacteria. However, when used as a cancer “vaccine,” it promotes an immune response that helps destroy the cancer, but it is not preventative, it is an adjuvant therapy called immunotherapy which is used along with chemotherapy, surgery, and radiation, as a part of the cancer treatment strategy. In other words, if you got the BCG vaccine for whatever reason, it does not make you “immune” to liver cancer.

Scientists are still working on why this vaccine, which is unrelated to any cancer, has this effect. Mostly, it is a nonspecific effect that seems to boost the immune system at a localized site, such as the liver. It might be some type of inflammatory response that boosts certain immune system regulators that weaken the cancer cells, allowing other therapies, such as chemotherapy work better.

BCG and liver cancer paper

In a paper published on 2 February 2024 in Advanced Science, Yu-Jui Yvonne Wan, Ph.D., UC Davis Department of Pathology and Laboratory Medicine, Davis, California, and colleagues examined the effect of the BCG vaccine on hepatocellular carcinoma (HCC), the most common form of liver cancer. They found that the vaccine significantly reduced liver tumor burden and prolonged the survival of mice with HCC.

This groundbreaking study is the first to demonstrate the promising effects of the BCG vaccine in treating liver cancer. They found that the vaccine reduced the growth and development of the cancer cells. HCC is very difficult to treat because it does not respond well to immunotherapy.

Getting into the weeds of how this vaccine might work, the researchers found that BCG promotes immune cell infiltration, including CD4+ and CD8+ T cells, along with M1 macrophages, which are important immune system components that can destroy cancer cells. In fact, this was happening even without other adjuvant cancer therapies such as chemotherapy.

According to Dr. Wan:

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.

Summary

Usually, I do not discuss animal studies because only 10% of animal research ever ends up being clinically useful to humans. I want to see large clinical studies to convince me that something works.

However, we have a lot of research that establishes that the nonspecific immune effects of the BCG vaccine make it promising as an adjuvant therapy to treat difficult cancers. As I wrote above, it’s already being used as a treatment for bladder cancer, and it may reverse type 1 diabetes.

I think this is an exciting research direction for certain cancers, and because the BCG vaccine is already approved by the FDA and is commercially available, it’s going to be easy to start a clinical trial for this type of liver cancer. Stay tuned.

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Michael Simpson

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