Abstract
Bacillus Calmette–Guérin (BCG), an attenuated vaccine from Mycobacterium bovis, was initially developed as an agent for vaccination against tuberculosis. BCG proved to be the first successful immunotherapy against established human bladder cancer and other neoplasms. The use of BCG has been shown to induce a long-lasting antitumor response over all other forms of treatment against intermediate, non-invasive muscle bladder cancer Several types of tumors may now be treated by releasing the immune response through the blockade of checkpoint inhibitory molecules, such as CTLA-4 and PD-1. In addition, Toll-Like Receptor (TLR) agonists and BCG are used to potentiate the immune response against tumors. Studies concerning TLR-ligands combined with BCG to treat melanoma have demonstrated efficacy in treating mice and patients This review addresses several interventions using BCG on neoplasms, such as Leukemia, Bladder Cancer, Lung Cancer, and Melanoma, describing treatments and antitumor responses promoted by this attenuated bacillus. Of essential importance, BCG is described recently to participate in an adequate microbiome, establishing an effective response during cell-target therapy when combined with anti-PD-1 antibody, which stimulates T cell responses against the melanoma. Finally, trained immunity is discussed, and reprogramming events to shape innate immune responses are addressed.
Highlights
Cancer is a leading cause of death, with about 9.6 million deaths and 18 million new cases worldwide [1]
The maturation and differentiation of dendritic cells (DCs) occur in professional antigen-presenting cells (APCs), which indirectly activates the functional differentiation of antigen-specific CD4+ T cells and stimulates the antigen’s cross-presentation to CD8+ T cells [97]
Bacillus Calmette–Guérin (BCG) heterologous effects are dependent on innate immunity, probably involving trained immunity
Summary
Cancer is a leading cause of death, with about 9.6 million deaths and 18 million new cases worldwide [1]. The study of Bacillus Calmette–Guérin (BCG) anti-tumor activity began in 1929 when Pearl (1929) [2] observed a lower frequency of cancer in necroscopy in patients with tuberculosis at Johns Hopkins Hospital. BCG is used as a vaccine obtained from an attenuated strain of Mycobacterium bovis, developed from an initially more virulent strain, and described by Calmette and Guérin (1908, Pasteur Institute) [9]. Developed initially as an attenuated agent for vaccination against tuberculosis, BCG has been described as responsible for the non-specific increase in the immune system’s activity responding to a variety of neoplasms, causing them to regress at experimental levels [11]. BCG was initially described as an agent that produces a potent intra-tumoral cellular inflammatory response that somehow would induce tumor-shrinking
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