Spanish researchers discover a therapy for lung cancer, based on the tuberculosis vaccine

2023-10-04 13:39:29

Researchers from the University of Zaragoza (UZ) have discovered an effective therapy against lung tumors, based on the live tuberculosis vaccine, BCG.

The live attenuated BCG vaccine, which celebrated a century of use in 2021, is currently the only vaccine available against tuberculosis. Furthermore, for more than four decades, BCG administered transurethral remains a first-line treatment for the treatment of high-risk non-invasive bladder cancer, precisely due to its high capacity to stimulate the immune system against tumors.

Throughout this history, BCG has been tested repeatedly as an immunotherapy against different types of cancer in addition to bladder cancer, including leukemia, melanoma or lung, in all cases without success.

In the work published this Wednesday by the prestigious magazine ‘Nature Communications’, the team of researchers from the University of Zaragoza, led by Nacho Aguiló, describe that a modification in the BCG administration route could be key to increase its effectiveness against lung tumors.

Researcher Nacho Aguiló and his team have shown that intravenous inoculation of BCG increases the survival of mice very significantly in different lung cancer models.

Furthermore, this protective effect is 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. In this case, in some tumor models used it is observed that the combination of both treatments leads to the cure of approximately 50 percent of the animals, without them showing a trace of tumor in the lungs at the end of the experiment.

The research team led by Nacho Aguiló has been studying 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.

Clearly associated with smoking, lung cancer represents one of the most frequent cancers worldwide, and is the one that causes the highest mortality associated with cancer, with approximately 25 percent of deaths due to this disease. Despite the advances in recent years in the fight against cancer, such as immunotherapy treatments, the overall survival of lung cancer patients 5 years after diagnosis remains low, less than 30 percent.

This often occurs because the tumors are or become resistant to treatments. For example, 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.

The results of this work show that the administration of BCG intravenously avoids precisely these mechanisms of tumor resistance, resensitizing tumors to the action of immunotherapy treatments that are used today in the clinic. This is because the mechanism through which BCG works is complementary to that of these current therapies.

BCG induces the activation of different types of immune cells involved in anti-tumor immunity, such as ‘natural killer’ cells – commonly called NK cells – or cytotoxic T lymphocytes. These two branches of immunity are the main cytotoxic cell types responsible for eliminating tumor cells. The fact that tumors have much more activated cytotoxic cells in the presence of BCG makes it much more difficult for them to prevent its action before being eliminated.

Furthermore, given the fact that this study proposes the inoculation of live – attenuated – bacteria intravenously, it is vitally important to demonstrate that this strategy is safe.

In this sense, the study published in ‘Nature Communications’ shows specific results where it is described that intravenous BCG is well tolerated, without any sign that could reflect acute or chronic toxicity in mice. As with any treatment in biomedicine, the demonstration that intravenous BCG is safe in preclinical animal models is a “key” step in its possible advancement to transfer it to future clinical development.

This study, coordinated from the University of Zaragoza, has been developed thanks to the contribution of different research groups, including the Health Research Institute of Aragon (IIS Aragón), Network Biomedical Research Centers: CIBERES and CIBERINFEC, the National Center of Cardiovascular Research (CNIC), the National Center for Biotechnology (CNB) and IdiPAZ (Madrid). In addition, this work has the support of the Spanish Association Against Cancer, the University of Zaragoza has reported.