100 years of Bacillus Calmette–Guérin immunotherapy: from cattle to COVID-19

Lobo, Niyati; Brooks, Nathan; Zlotta, Alexandre R.; Cirillo, Jeffrey D.; Boorjian, Stephen A.; Black, Peter C.; Meeks, Joshua J.; Bivalacqua, Trinity J.; Gontero, Paolo; Steinberg, Gary D.; McConkey, David J.; Babjuk, Marko; Witjes, J. Alfred; Kamat, Ashish M.

doi:10.1038/s41585-021-00481-1

Cited by 100 publications

(71 citation statements)

References 153 publications

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“…This is consistent with recent data reported by Rivas and coworkers [71] and discussed in detail elsewhere [72] , indicating that history of BCG vaccination is associated with a decrease in the seroprevalence of anti-SARS-CoV-2 IgG and a lower number of subjects experiencing COVID-19-related clinical symptoms in a cohort of health-care workers. Notably, current studies are also based on the use of recombinant BCG activating the STING pathway to enhance the potency of the immune response [73] . While the interim results of the “ACTIVE” clinical trial aimed at evaluating the efficacy of BCG vaccination in protecting elderly patients against new infections seem to be encouraging [74] , more data are needed to eventually confirm whether BCG vaccination, alone or in combination, can indeed exert a protective effect against SARS-CoV-2 infection.…”

Section: Fostering Innate Antiviral Immunity For the Control Of Pandemic Viruses: Role Of Type I Ifnmentioning

confidence: 99%

Exploiting natural antiviral immunity for the control of pandemics: Lessons from Covid-19

Aricò

Bracci

Castiello

et al. 2022

Cytokine & Growth Factor Reviews

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The outbreak of coronavirus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the disruptive global consequences in terms of mortality and social and economic crises, have taught lessons that may help define strategies to better face future pandemics. Innate and intrinsic immunity form the front-line natural antiviral defense. They involve both tissue-resident and circulating cells, which can produce anti-viral molecules shortly after viral infection. Prototypes of these factors are type I interferons (IFN), antiviral cytokines with a long record of clinical use. During the last two years, there has been an impressive progress in understanding the mechanisms of both SARS-CoV-2 infection and the cellular and soluble antiviral responses occurring early after viral exposure. However, this information was not sufficiently translated into therapeutic approaches. Insufficient type I IFN activity probably accounts for disease progression in many patients. This results from both the multiple interfering mechanisms developed by SARS-CoV-2 to decrease type I IFN response and various pre-existing human deficits of type I IFN activity, inherited or auto-immune. Emerging data suggest that IFN-I-mediated boosting of patients’ immunity, achieved directly through the exogenous administration of IFN-β early post viral infection, or indirectly following inoculation of heterologous vaccines (e.g. Bacillus Calmette Guerin), might play a role against SARS-CoV-2. We review how recent insights on the viral and human determinants of critical COVID-19 pneumonia can foster clinical studies of IFN therapy. We also discuss how early therapeutic use of IFN-β and prophylactic campaigns with live attenuated vaccines might prevent a first wave of new pandemic viruses.

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Section: Fostering Innate Antiviral Immunity For the Control Of Pandemic Viruses: Role Of Type I Ifnmentioning

confidence: 99%

Exploiting natural antiviral immunity for the control of pandemics: Lessons from Covid-19

Aricò

Bracci

Castiello

et al. 2022

Cytokine & Growth Factor Reviews

View full text Add to dashboard Cite

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“…Recently a multi-center retrospective cohort study including 12,185 bladder cancer patients with a follow-up of 3.5 to 7 years shows that the 2301 BCG-treated patients manifested more than 4-fold less risk for AD than those not treated with BCG [ 42 , 43 ]. On the other hand, the antituberculosis vaccine bacillus Calmette-Guérin (BCG) appears as preventative of the severity of coronavirus disease 2019 (COVID-19) [ 44 , 45 ]. From a life-course perspective, the role of infant vaccinations and boosters is fundamentally important in contributing to maintaining good health well into adulthood.…”

Section: At the Individual Level The Other Benefits Of Vaccines Are L...mentioning

confidence: 99%

The Implications of Vaccines in Older Populations

Michel

Frangos

2022

Vaccines

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Mean longevity is increasing worldwide, with major consequences for public health worldwide, as the global population of adults aged over 65 years now exceeds the number of children under 5 for the first time in history. The ageing process over the life course is extremely heterogeneous, and it will be important to promote and enhance healthy ageing worldwide. Vaccination is a key player in the healthy ageing process, both at the individual and the community level. We review here the contribution of vaccines to individual and community health. At an individual level, we highlight the prevention of infectious diseases, as well as other, less well-known benefits of vaccination, such as modulation of the inflammatory process. We then underline the importance of vaccination in achieving herd immunity and reducing the transmission of pathogens in the community. Finally, at a community level, another important benefit of vaccination is the reduction in antimicrobial resistance. Taken together, these effects contribute to ensuring the best health, for the greatest number, for the longest time possible.

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“…Though BCG has been used for decades, the mechanisms of action and failure are not fully understood. Despite of high initial response rates, a study found that up to 42% of patients recurred after complete BCG-therapy, and 14% progressed 2,3 BCG is thought to act through activation of both the innate and adaptive immune systems, thereby promoting lasting antitumor effects 4 . Several immune cell types have proven necessary for BCG-response in vitro and in murine studies, including natural killer (NK) cells 5 , neutrophils 6 , and T-cells 7 .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated T-cell exhaustion and urinary tumor DNA levels are associated with BCG failure in patients with non-muscle invasive bladder cancer

Strandgaard

Lindskrog

Nordentoft

et al. 2022

Preprint

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BackgroundThe functional status of immune cells within the tumor microenvironment and tumor characteristics may explain Bacillus Calmette-Guérin (BCG)-failure in high-risk non-muscle invasive bladder cancer (NMIBC).ObjectiveTo characterize molecular correlates of BCG-failure using a multiomics approach.Design, Setting, and ParticipantsBCG-treated NMIBC patients (n=156) were included. Metachronous tumors were analyzed using RNA-sequencing (n=170) and whole exome sequencing (n=198). Urine samples were analyzed for immune-oncology related proteins (n=190), and tumor-derived DNA (tdDNA; n=192).Outcome Measurement and Statistical AnalysisPrimary endpoint was BCG-failure. Cox regression, Wilcoxon Rank Sum test, t-test or Fisher’s exact test were used.Results and LimitationsBCG caused activation of the immune system regardless of clinical response; however, immune-inhibitory proteins were observed in the urine of BCG-unresponsive patients post-treatment (CD70, PD1, CD5). BCG-failure was associated with post-BCG T-cell exhaustion (p=0.0021). Pre-BCG tumors from patients with post-BCG T-cell exhaustion were characterized by high expression of cell division and immune-related genes. A high post-BCG exhaustion prediction score in pre-BCG tumors was associated with worse post-BCG high-grade recurrence free survival (HGRFS), reflecting BCG-failure (p=0.0084). Pre-BCG tumors of class 2a and 2b were likewise associated with worse post-BCG HGRFS(p=0.0023). Post-BCG exhaustion was observed in patients with high pre-BCG neoantigen load (p=0.023) and mutations in MUC4 (p=0.0007). Finally, absence of post-BCG tdDNA clearance identified patients at high risk of recurrence (p=0.028). The retrospective design, lack of maintenance BCG, and partial overlap in analyses are limitations to the study.ConclusionsBCG failure may be caused by T-cell exhaustion. Tumor subtype and Pre-BCG tumor characteristics may identify patients at high risk of BCG-failure prior to treatment. Urinary measurements have the potential to be used as a real-time assessment of treatment response.Patient SummaryA dysfunctional immune response to BCG therapy may explain lack of response to the treatment.

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100 years of Bacillus Calmette–Guérin immunotherapy: from cattle to COVID-19

Cited by 100 publications

References 153 publications

Exploiting natural antiviral immunity for the control of pandemics: Lessons from Covid-19

Exploiting natural antiviral immunity for the control of pandemics: Lessons from Covid-19

The Implications of Vaccines in Older Populations

Elevated T-cell exhaustion and urinary tumor DNA levels are associated with BCG failure in patients with non-muscle invasive bladder cancer

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