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      Bacillus Calmette-Guérin (BCG) Therapy for Bladder Cancer: An Update

      review-article
      1 , 1
      ImmunoTargets and Therapy
      Dove
      mycobacteria, nonmuscle invasive, immunotherapy, alternative treatment

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          Abstract

          Physicians treating patients affected by nonmuscle-invasive bladder cancer (NMIBC) have been in shock during the last six years since manufacturing restrictions on the production of the first-option medicine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), have resulted in worldwide shortages. This shortage of BCG has led to a rethinking of the established treatment guidelines for the rationing of the administration of BCG. Some possible schedule modifications consist of a decrease in the length of maintenance treatment, a reduction in the dose of BCG in intravesical instillations or the use of different BCG substrains. All these strategies have been considered valuable in times of BCG shortage. In addition, the lack of availability of BCG has also led to the general recognition of the need to find new treatment options for these patients so that they are not dependent on a single treatment. Few alternatives are committed to definitively replacing BCG intravesical instillations, but several options are being evaluated to improve its efficacy or to combine it with other chemotherapeutic or immunotherapeutic options that can also improve its effect. In this article, we review the current state of the treatment with BCG in terms of all of the aforementioned aspects.

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          Side effects of Bacillus Calmette-Guérin (BCG) in the treatment of intermediate- and high-risk Ta, T1 papillary carcinoma of the bladder: results of the EORTC genito-urinary cancers group randomised phase 3 study comparing one-third dose with full dose and 1 year with 3 years of maintenance BCG.

          Although bacillus Calmette-Guérin (BCG) has proven highly effective in non-muscle-invasive bladder cancer (NMIBC), but it can cause severe local and systemic side effects.
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            The Recombinant Bacille Calmette–Guérin Vaccine VPM1002: Ready for Clinical Efficacy Testing

            The only licensed vaccine against tuberculosis (TB), bacille Calmette–Guérin (BCG), protects against severe extrapulmonary forms of TB but is virtually ineffective against the most prevalent form of the disease, pulmonary TB. BCG was genetically modified at the Max Planck Institute for Infection Biology to improve its immunogenicity by replacing the urease C encoding gene with the listeriolysin encoding gene from Listeria monocytogenes. Listeriolysin perturbates the phagosomal membrane at acidic pH. Urease C is involved in neutralization of the phagosome harboring BCG. Its depletion allows for rapid phagosome acidification and promotes phagolysosome fusion. As a result, BCGΔureC::hly (VPM1002) promotes apoptosis and autophagy and facilitates release of mycobacterial antigens into the cytosol. In preclinical studies, VPM1002 has been far more efficacious and safer than BCG. The vaccine was licensed to Vakzine Projekt Management and later sublicensed to the Serum Institute of India Pvt. Ltd., the largest vaccine producer in the world. The vaccine has passed phase I clinical trials in Germany and South Africa, demonstrating its safety and immunogenicity in young adults. It was also successfully tested in a phase IIa randomized clinical trial in healthy South African newborns and is currently undergoing a phase IIb study in HIV exposed and unexposed newborns. A phase II/III clinical trial will commence in India in 2017 to assess efficacy against recurrence of TB. The target indications for VPM1002 are newborn immunization to prevent TB as well as post-exposure immunization in adults to prevent TB recurrence. In addition, a Phase I trial in non-muscle invasive bladder cancer patients has been completed, and phase II trials are ongoing. This review describes the development of VPM1002 from the drawing board to its clinical assessment.
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              Bacillus Calmette-Guérin strain differences have an impact on clinical outcome in bladder cancer immunotherapy.

              Whether the commonly used bacillus Calmette-Guérin (BCG) strains Connaught and Tice confer different treatment responses in non-muscle-invasive bladder cancer (NMIBC) is unknown.
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                Author and article information

                Journal
                Immunotargets Ther
                Immunotargets Ther
                ITT
                itt
                ImmunoTargets and Therapy
                Dove
                2253-1556
                13 February 2020
                2020
                : 9
                : 1-11
                Affiliations
                [1 ]Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona , Bellaterra (Barcelona), Spain
                Author notes
                Correspondence: Esther Julián Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona , Bellaterra (Barcelona), SpainTel +34 93 5814870Fax +34 93 5812387 Email esther.julian@uab.cat
                Author information
                http://orcid.org/0000-0002-9666-5757
                http://orcid.org/0000-0002-6558-3978
                Article
                202006
                10.2147/ITT.S202006
                7025668
                32104666
                49f5886d-47e1-4620-b5a4-9461e8fdb164
                © 2020 Guallar-Garrido and Julián.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 19 December 2019
                : 28 January 2020
                Page count
                Figures: 1, Tables: 1, References: 89, Pages: 11
                Categories
                Review

                mycobacteria,nonmuscle invasive,immunotherapy,alternative treatment

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