Building on a Solid Foundation: Enhancing Bacillus Calmette-Guérin Therapy

Rentsch, Cyrill A.; Derré, Laurent; Dugas, Sarah G.; Wetterauer, Christian; Federer-Gsponer, Joël R; Thalmann, George N.; Ingersoll, Molly A.

doi:10.1016/j.euf.2018.10.010

Cited by 10 publications

(6 citation statements)

References 89 publications

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“…UC is well recognized as an immunogenic and immunoresponsive tumor. Intravesicle bacillus calmette-Guerin (BCG) has been widely used in non-muscle-invasive bladder cancer for more than 40 years with superior efficacy 28,29 . Genome wide studies have also demonstrated that UC has the fourth highest overall mutational burden, which can consequently triggers immune responses 28 .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of PD-L1 and other immune markers in bladder urothelial carcinoma stratified by histologic variants and molecular subtypes

Zhang

Shuman

et al. 2020

Sci Rep

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Although advanced bladder cancer overall has a poor prognosis, a subset of patients demonstrate durable response to immune checkpoint inhibitors. Evidence shows that the response to checkpoint inhibitors may be associated with type and degree of immune infiltration in the tumor microenvironment. Here, we evaluated immune markers stratified by molecular subtypes and histologic variants. The study utilized a series of urothelial carcinomas (UCs) by tissue microarray, on which histologic variants and molecular subtypes had previously been established. PD1, CD3, CD8 and CD68 expression was evaluated by immunohistochemistry in tumor infiltrating immune cells, while PD-L1 expression in the tumor microenvironment was assessed. Each marker was scored semi-quantitatively (score 0-3). Tumors were clustered by marker scores using agglomerative methods, and associations among markers, histologies, and molecular subtypes were analyzed. PD-L1 expression in the tumor microenvironment significantly correlated with presence of CD3, CD8 and chronic inflammation. Urothelial carcinoma may be classified as either immune high or low based on marker expression. The immune high group is enriched in higher CD3, PD-L1, and genomically-unstable molecular subtype, suggesting it may respond to checkpoint inhibitors. We also identified a degree of intratumoral heterogeneity in immune markers in bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Evaluation of PD-L1 and other immune markers in bladder urothelial carcinoma stratified by histologic variants and molecular subtypes

Zhang

Shuman

et al. 2020

Sci Rep

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“…Experimental models have suggested that either a PPD + state before the start of treatment or conversion from a PPD À to PPD + state during treatment might predict response to therapy [18]. In clinical trials, the clinical correlation between PPD status and outcome has been conflicted by heterogeneous results, by previous mycobacterial exposure, and different handling in the execution and interpretation of the test itself [19]. In SAKK 06/14, most patients (77.5%) had a negative PPD test before the start of their treatment with VPM1002BC, although they had previously been exposed to BCG.…”

Section: Ppd Testingmentioning

confidence: 99%

A Phase 1/2 Single-arm Clinical Trial of Recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC Immunotherapy in Non–muscle-invasive Bladder Cancer Recurrence After Conventional BCG Therapy: SAKK 06/14

Rentsch

Thalmann

Lucca³

et al. 2022

European Urology Oncology

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Background: VPM1002BC is a genetically modified Mycobacterium bovis bacillus Calmette-Guérin (BCG) strain with potentially improved immunogenicity and attenuation. Objective: To report on the efficacy, safety, tolerability and quality of life of intravesical VPM1002BC for the treatment of non-muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG therapy. Design, setting, and participants: We designed a phase 1/2 single-arm trial (NCT02371447). Patients with recurrent NMIBC after BCG induction ± BCG maintenance therapy and intermediate to high risk for cancer progression were eligible. Intervention: Patients were scheduled for standard treatment of six weekly instillations with VPM1002BC followed by maintenance for 1 yr. Treatment was stopped in cases of recurrence. Outcome measurements and statistical analysis: The primary endpoint was defined as the recurrence-free rate (RFR) in the bladder 60 wk after trial registration. The sample size was

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“…Indeed, BCG is already known to have protective and therapeutic effects beyond the prevention of infection with tuberculosis. These effects include reduced susceptibility to nonmycobacterial infections [12][13][14], therapeutic effects in bladder cancer (when administered as an intravesical infusion) [15] and a reduced incidence of early mortality [16,17]. These effects appear to be mediated through both adaptive immunity and innate immune responses known as 'trained immunity'.…”

Section: Review Symposiummentioning

confidence: 99%

Benefits of BCG‐induced metabolic switch from oxidative phosphorylation to aerobic glycolysis in autoimmune and nervous system diseases

Faustman

2020

J. Intern. Med.

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The most commonly used vaccine worldwide, bacillus Calmette–Guerin (BCG), appears to have the ability to restore blood sugar control in humans with early‐onset but long‐duration type 1 diabetes when a repeat vaccination strategy is used. This is a process that may be driven by a metabolic switch from overactive oxidative phosphorylation to accelerated aerobic glycolysis and a reset of the immune system. BCG is a live, attenuated strain of Mycobacteria bovis, a cousin of M. tuberculosis. Humans and Mycobacteria, which are found in the environment and in warm‐blooded hosts, share a long coevolutionary history. In recent times, humans have had fewer exposures to these and other microorganisms that historically helped shape the immune response. By ‘re‐introducing’ an attenuated form of Mycobacteria via BCG vaccination, humans might benefit from an immunological perspective, a concept supported by a growing body of data in autoimmunity and robust data on the nonspecific immune effects of BCG related to protection from diverse infections and early mortality. New findings of immune and metabolic defects in type 1 diabetes that can be corrected with repeat BCG vaccination suggest that this therapeutic strategy may be applicable in other diseases with inadequate aerobic glycolysis, including Parkinson’s disease, dementia, depression and other disorders affecting the nervous system.

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Building on a Solid Foundation: Enhancing Bacillus Calmette-Guérin Therapy

Cited by 10 publications

References 89 publications

Evaluation of PD-L1 and other immune markers in bladder urothelial carcinoma stratified by histologic variants and molecular subtypes

Evaluation of PD-L1 and other immune markers in bladder urothelial carcinoma stratified by histologic variants and molecular subtypes

A Phase 1/2 Single-arm Clinical Trial of Recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC Immunotherapy in Non–muscle-invasive Bladder Cancer Recurrence After Conventional BCG Therapy: SAKK 06/14

Benefits of BCG‐induced metabolic switch from oxidative phosphorylation to aerobic glycolysis in autoimmune and nervous system diseases

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