The Aragonese vaccine against tuberculosis could be effective against bladder cancer

The Aragonese vaccine against tuberculosis could be effective against bladder cancer

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The live attenuated vaccine against tuberculosis Mtvbac, built at the University of Zaragoza and developed by the Galician company Biofabri belonging to the Zendal group, and which is soon expected to begin phase III efficacy studies in babies in South Africa, could have applications to treat diseases beyond tuberculosis. This is the case of non-muscle invasive bladder cancer resistant to the current treatment with the BCG vaccine, a disease for which the researcher from the University of Zaragoza Nacho Aguiló and his group have shown in an experimental model in mice that Mtvbac is highly efficient, as and as can be deduced from the results of the research published in the prestigious Journal for ImmunoTherapy of Cancer.

Bladder cancer represents the 5th most frequent type of cancer in developed countries, with an incidence three times higher in men than in women. In the case of non-muscle invasive bladder cancer, this represents around 70% of bladder cancer cases, and many of these patients are currently treated by successive intravesical applications of the current tuberculosis vaccine, the BCG, whose mechanism consists of stimulating the immune system against the tumor.

This treatment has been administered with hardly any changes since the end of the 1970s, when the Colombian doctor living in Canada, Álvaro Morales, successfully tested BCG for the first time in patients with bladder cancer, being the first immunotherapy against cancer approved by the US drug agency, the FDA, in 1990. However, although BCG remains the treatment of choice for high-risk non-muscle invasive bladder tumors, one of the main problems with this therapy is that there are a number A significant number of patients who do not respond to treatment are called BCG-resistant patients. In this case, the possibilities of treating these patients are very limited, and in most cases the only effective alternative is direct removal of the bladder (cystectomy), a major surgical procedure that seriously affects the quality of life of patients. patients. It is therefore a priority in the field of urology Scientific Culture Unit 660 010 349 [email protected] the development of effective therapies for the treatment of patients refractory to BCG.

The study published today in the Journal for ImmunoTherapy of Cancer shows that Mtvbac could be a plausible alternative for the treatment of BCG-resistant bladder cancer. The results showed the total elimination of the tumors in more than 60% of the Mtvbac-treated mice, while these were not rejected in any of the BCG-treated animals. When a combination therapy of MTBVAC was applied together with monoclonal antibodies directed at blocking the pro-tumor molecule PD-L1 (which is one of the main types of immunotherapy currently used against cancer), it resulted in a 100% survival rate. the animals to which the double therapy was administered. In addition, no adverse effects were observed in any of the treated animals, and the fact that MTBVAC is a vaccine whose safety has been studied in humans, and that it is produced at an industrial level by the Biofabri company, would represent a great advantage for its possible application in the clinic, so it would be a priority to try to accelerate clinical studies in patients in whom BCG treatment has failed.

This study, coordinated from the University of Zaragoza, has been carried out thanks to the contribution of different national and international groups, including the Aragón Health Research Institute (IIS Aragón), Network Biomedical Research Centers: Ciberes and Ciberinfec, the Center National Center for Cardiovascular Research (CNIC), the National Center for Biotechnology (CNB) and the University Hospital of Vaud, in Lausanne (Switzerland). In addition, it has had the contribution of the pharmaceutical company Biofabri, industrial and clinical developer of the Mtvbac vaccine.

The research team led by Nacho Aguiló has been investigating the use of tuberculosis vaccines in preclinical cancer models for years. In the particular case of bladder cancer, in 2018 the team led by Nacho Aguiló demonstrated for the first time that MTBVAC was effective against bladder tumors in mice. Now the results go further, showing that Mtvbac is qualitatively superior to the current treatment used in the clinic, the BCG vaccine.

This work is included in the doctoral thesis of Eduardo Moreo, first author of the study, developing an experimental model of bladder cancer where the different treatments administered transurethrally can be tested in vivo. The results of the article published today also characterize in detail the immunological mechanism through which the Mtvbac vaccine rejects tumors. Mtvbac, and not BCG, induces a tumor-specific T-type immune response, which is capable of rejecting not only tumors in the bladder, but also tumors themselves when they spread to other organs such as the lungs, suggesting that this response could be effective in preventing metastatic events that occur in advanced stages of bladder cancer.

The current BCG vaccine, based on a live attenuated form of Mycobacterium bovis isolated from cows and which turned a century

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