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Artículo Tomo 71, Número. 4, Mayo 2018

Archivos Españoles de Urología

Mechanism of action of intravesical BCG. Biological bases and clinical applicability.

Authors: Joaquín A. Carballido y María Rodríguez Monsalve.

Arch. Esp. Urol. 2018; 71 (4): 358-375

Vol. 71, Number. 4, May 2018

The therapeutic approaches developed around immune system modulation find the therapeutic contribution of intravesical Bacillus Calmette Guerin (BCG) for transitional cell bladder cancer an unquestionable example as a proof of concept of antitumor immunotherapy since more than 30 years ago. Intravesical immunotherapy for urothelial carcinomas is considered with periodic intravesical instillations schedules, and the one with longer historic development and wider diffusion is BCG in the form of suspension. BCG is a unique strain obtained from Mycobacterium bovis at the end of the first third of the XX century and represents the historically most successful immunotherapeutic modality of all tumors with a high level body of evidence. Currently, we even see an unpredictable development potential of this therapeutic modality based on immunomodulation related with activation or suppression of T lymphocytes by blocking the immune system checkpoints. This option is at this time a decisive step in the treatment of chemotherapy refractory metastatic urothelial carcinoma. Over the last years, there have been advances in the intimate mechanism of action of intravesical BCG, but there are many open questions that will only be answered from complex basic and translational research platforms. The objective of this review article is to try to translate the basic mechanisms currently implicated in the different phases of antitumor response of BCG in its routine use in clinical practice. Also, to analyze the future lines already active under clinical research with and without implications of the mechanisms of action of BCG. We describe the role of interactions basally established between urothelial tumor cells and cellular and molecular elements of the immune system of the patients with ulterior antitumor effector capacity. After intravesical BCG therapy and its interaction, we describe the various phases of its mechanism of action, namely fixation, internalization and triggering of the lytic cytotoxic antitumor response, and its integration in the current intravesical treatment regimens The implication of all these mechanisms in the varied capacity of clinical response observed in patients, reviewing the current status of knowledge of BCG mechanisms of action, leads unavoidably to the search of better clinical efficacy through eventual immune response markers and to set the approach to the knowledge of the individual reactivity of the immune system of each patient as a determinant factor to be able to adopt adjusted therapeutic patterns.

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