The live attenuated BCG vaccine that has been used for a hundred years against tuberculosis is also administered transurethally as a treatment for high-risk non-invasive bladder cancer because it has a high capacity to stimulate the immune system against tumors. This drug has also been tested as an immunotherapy to combat other types of cancer, such as leukemia, melanoma or lung cancer, although without success.
However, researchers from the University of Zaragoza have found a way to increase the therapeutic efficacy of this vaccine in the case of lung cancer, and in a study they have published in Nature Communications they explain that a modification in the BCG administration route could be essential to increase its effectiveness against lung tumors.
Currently, lung cancer is one of the most common cancers in the world, and it causes the highest cancer mortality. Despite advances such as immunotherapy treatments, the overall survival of lung cancer patients five years after diagnosis is still less than 30%. And this is due, in part, to the fact that tumors are or become resistant to treatments. For example, the researchers explain, “it is very common for tumor cells to learn to immunosuppress the action of the immune system, making immunotherapy based on checkpoint inhibitors currently used ineffective.”
BCG intravenously promotes the elimination of tumor cells
Researcher Nacho Aguiló and his team have shown that intravenous inoculation of BCG significantly increased the survival of mice in different lung cancer models. This protective effect was especially evident when the use of BCG was combined with checkpoint inhibitors, such as the anti-PD-L1 molecule – one of the most used immunotherapies currently in oncology – since they observed that in some tumor models When used, the combination of both treatments led to the cure of around 50% of the animals, without them showing traces of tumor in the lungs at the end of the experiment.
Intravenous inoculation of BCG significantly increased the survival of mice in different lung cancer models
The research team led by Nacho Aguiló has been investigating the use of tuberculosis vaccines as immunotherapy in preclinical cancer models for years. This work is included in the doctoral thesis of Eduardo Moreo, first author of the study, which aimed to develop experimental models of lung cancer that allowed the BCG vaccine administered intravenously to be tested in vivo.
The results of this work show that the intravenous administration of BCG precisely avoids these mechanisms of tumor resistance, making tumors once again sensitive to the action of the immunotherapy treatments currently used. This is because the mechanism through which BCG works is complementary to that of these therapies.
Specifically, BCG induces the activation of different types of immune cells that are involved in antitumor immunity, such as “natural killer” cells (or commonly called NK cells) or cytotoxic T lymphocytes. These two branches of immunity are the main cytotoxic cell types responsible for eliminating tumor cells. When tumors encounter cytotoxic cells that are much more activated in the presence of BC, it is much more difficult for them to prevent their action before being eliminated.
Furthermore, given that this study proposes the inoculation of live (attenuated) bacteria intravenously, it is vitally important to demonstrate the safety of this strategy. In this sense, the study shows specific results where it is described that intravenous BCG is well tolerated, without any sign that could reflect acute or chronic toxicity in the mice. As with any treatment in biomedicine, demonstration that intravenous BCG is safe in preclinical animal models is a key step in its potential translational advancement toward future clinical development.
Source: University of Zaragoza
