In February 2024 UC Davis Health announced the results of a study, published in Advanced Science, which show that a single dose of the tuberculosis vaccine Bacillus Calmette-Guérin (BCG) reduced liver tumour burden and extended the survival of mice with liver cancer. BCG is known for “immune-boosting properties”, but this trial found that it could be a “promising treatment option” for hepatocellular carcinoma (HCC), which is often “associated with unfavourable treatment outcomes”.
HCC: significant challenges
The study describes hepatocellular carcinoma (HCC) as a “common” liver cancer that causes “numerous deaths” globally. Although conventional systemic cytotoxic chemotherapeutic agents, protein kinase inhibitors, and immunotherapy options exist, HCC “continues to pose significant challenges in terms of treatment”. Therefore, the authors identify a “pressing need” for alternative therapeutic approaches.
Distinguished Professor Yu-Jui Yvonne Wan, vice chair for research in the Department of Pathology and Laboratory Medicine at UC Davis, commented that “HCC is very difficult to treat”. It is “considered a cold tumour, which does not respond well to immunotherapy”. However, Professor Wan’s team had “a good reason to believe that the BCG vaccine could stimulate an immune response”.
BCG
BCG, derived from live attenuate Mycobacterium bovis, has been used as the primary tuberculosis vaccine since the 1920s. Although it has specific effects against tuberculosis, it has “non-specific effects”. These could be attributed to trained immunity.
BCG was approved by the FDA for the treatment of non-muscle invasive bladder cancer, which involves the administration of BCG directly into the bladder. However, there is “limited information available regarding the potential therapeutic effect of BCG” in the treatment of other solid tumours. Therefore, authors conducted a study to investigate the anti-HCC effects of BCG in orthotopic HCC mouse models.
A positive response
The researchers found that BCG reduced inflammation and encouraged the deployment of T cells, specifically allowing the infiltration of CD4+ and CD8+ T cells and M1 macrophages into the tumour. BCG also induced IFN- γ signalling, which resulted in cancer cell death. Furthermore, Professor Wan states that “while previous studies have shown sex differences in BCG effects on immunity”, the data indicate that “both male and female HCC mice responded to the BCG treatment”.
“Our study showed that BCG immunotherapy for HCC is different from and superior to other immunotherapies. It requires only a single injection. In animal models, BCG generated better anti-liver cancer treatment outcomes than other standard immunotherapies, such as anti-PD-1.”
The authors conclude that the study offers “compelling evidence” in support of BCG treatment for HCC. Additionally, because it is “widely used with a known safety profile”, BCG bacterial immunotherapy “should be considered for HCC as well as other solid cancers”.
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