Bacillus Calmette–Guérin strain differences as the basis for immunotherapies against bladder cancer

Miyazaki, Jun; Onozawa, Mizuki; Takaoka, Eiichiro; Yano, Ikuya

doi:10.1111/iju.13538

Cited by 22 publications

(11 citation statements)

References 70 publications

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“…As preservation methods for live bacteria had not been developed, the first BCG Pasteur strain had been serially passaged over many times within years, which led to its divergence and worldwide distribution of several genetically distinct daughter strains [23,24]. After the development of lyophilization, each daughter strain was preserved and named after its site of origin [24].…”

Section: Introductionmentioning

confidence: 99%

Clinical and molecular insights into BCG immunotherapy for melanoma

2020

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The incidence of cutaneous melanoma and the mortality rate of advanced melanoma patients continue to rise globally. Despite the recent success of immunotherapy including ipilimumab and pembrolizumab checkpoint inhibitors, a large proportion of patients are refractory to such treatment modalities. The application of mycobacteria such as Bacillus Calmette–Guérin (BCG) in the treatment of various malignancies, including cutaneous melanoma, has been clearly demonstrated after almost a century of observations and experimentation. Intralesional BCG (IL‐BCG) immunotherapy is a highly efficient and cost‐effective treatment option for inoperable stage III in‐transit melanoma, as recommended in the National Comprehensive Cancer Network Guidelines. IL‐BCG has shown great efficacy in the regression of directly injected metastatic melanoma lesions, as well as distal noninjected nodules in immunocompetent patients. Clinical and preclinical studies have shown that BCG serves as a strong immune modulator, inducing the recruitment of various immune cells that contribute to antitumour immunity. However, the specific mechanism of BCG‐mediated tumour immunity remains poorly understood. Comparative genome analyses have revealed that different BCG strains exhibit distinct immunological activity and virulence, which might impact the therapeutic response and clinical outcome of patients. In this review, we discuss the immunostimulatory potential of different BCG substrains and highlight clinical studies utilizing BCG immunotherapy for the treatment of cutaneous melanoma. Furthermore, the review focuses on the cellular and molecular mechanisms of the BCG‐induced immune responses of both the innate and adaptive arms of the immune system. Furthermore, the review discussed the administration of BCG as a monotherapy or in combination with other immunotherapeutic or chemotherapeutic agents.

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Section: Introductionmentioning

confidence: 99%

Clinical and molecular insights into BCG immunotherapy for melanoma

2020

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“…The treatment and molecular mechanism of various cancers are still unclear (20,21). There have been numerous reports of BCG inhibited development of bladder cancer and intestinal carcinoma (22,23). BCG administration would be an effective local adjuvant therapy following radical surgery to treat patients with gastrointestinal cancer, but its effect on gastric cancer and the mechanism are still not clear (14,24,25).…”

Section: Discussionmentioning

confidence: 99%

“…BCG can not only induce cancer cells to express antigens that can stimulate specific immune responses, including tumor-associated antigens and cross-reactive antigens such as heat shock proteins, but also induce cancer cells to express adhesion molecules (such as ICAM-1) and Fas receptors, thereby enhancing the binding of immunocompetent effector cells to cancer cells, and inducing cancer cell apoptosis through Fas-fasl and perforin (23). After intravesical infusion of BCG, cancer cells can express major histocompatibility com- plex-II molecules (MHC-II) (26).…”

Section: Discussionmentioning

confidence: 99%

Bacillus Calmette Guérin (BCG) activates lymphocyte to promote autophagy and apoptosis of gastric cancer MGC-803 cell

Yao

Wang

et al. 2018

Cell Mol Biol (Noisy-le-grand)

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Bacillus Calmette Guérin (BCG) has a potential anti-tumor effect on gastric cancer. However, the mechanism is still unclear. In this study, we investigated the effect of BCG on gastric cancer cell line MGC-803 and studied the potential cooperation of BCG and lymphocyte in determining the final fate of cancer cells. After treatment with BCG, the cell viability was significantly inhibited in a dosage-dependent manner. Flow cytometry assay showed the apoptosis rates were significantly increased by BCG. Using western blot assay, results showed that BCG increased cleaved-caspase-3, LC-3BII and Atg-3. After cocultured with BCG and lymphocyte, the apoptosis rates, the levels of cleaved-caspase-3, and the protein levels of LC-3BII and Atg-3 were significantly increased compared with BCG or lymphocytes alone groups. ELISA detection found that BCG induced secretion of interferon gamma (IFNg) from lymphocytes. BCG with IFNg also increased levels of cleaved-caspase-3, LC-3BII and Atg-3. Taken together, BCG promotes lymphocyte immunocompetence to induce cell apoptosis and autophagy in MGC-803 cells, might through inducing release of IFNg from peripheral blood lymphocytes.

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“…Results of randomized trials and observational studies pertaining to all-cause mortality and morbidity associated with BCG administration are shown in Table 1. While the nature of the BCG strains might, to some extent, explain differences between studies (Miyazaki et al 2018;Curtis 2019), the majority of results suggest that BCG provides significant protection against non-mycobacterial infections. The most interesting of these studies is the recent RCT carried out in Greece and showing a significant 79% protection against all-cause non-TB infection over a 12-month period (Giamarellos-Bourboulis et al 2020).…”

Section: Human Studies On "Off Target" Protection Of Bcg Vaccinationmentioning

confidence: 99%

Can BCG be useful to mitigate the COVID-19 pandemic? A Canadian perspective

Wals

Menzies

Divangahi

2020

Can J Public Health

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There is ample evidence from in vitro, animal and human studies that the Bacillus Calmette-Guerin (BCG) vaccine epigenetically reprograms innate immunity to provide "off target" protection against pathogens other than mycobacteria. This process has been termed "trained immunity". Although recent ecological studies suggested an association between BCG policies and the frequency or severity of COVID-19 in different countries, the interpretation of these results is challenging. For this reason, a case-control study aiming to test this hypothesis has been initiated in Quebec. Several phase III clinical trials are underway, including one in Canada, to assess the efficacy of BCG against SARS-CoV-2 infection (results expected in 2021). In the past, BCG has been widely used in Canada but current indications are restricted to high-risk individuals and communities experiencing TB outbreaks as well as for the treatment of bladder cancer. The potential implication of BCG as an interim measure to mitigate COVID-19 is the subject of widespread discussion in the scientific community and can be considered for the vulnerable population in Canada. To conclude, BCG vaccination should be placed on the agenda of research funding agencies, scientific advisory committees on immunization and federal/provincial/territorial public health authorities. Résumé Il existe de nombreuses preuves issues d'études in vitro, chez l'animal et chez l'humain qui montrent que le vaccin bacillaire de Calmette et Guérin (BCG) peut reprogrammer de manière épigénétique l'immunité naturelle et procurer ainsi une protection « hors-cible » contre des pathogènes autres que les mycobactéries. Ce processus a été appelé « immunité entraînée ». Bien que des études écologiques récentes aient suggéré l'existence d'une association entre les politiques d'utilisation du BCG et la fréquence ou sévérité de la COVID-19 dans différents pays, l'interprétation de leurs résultats est difficile. Pour cette raison, une étude castémoin a été entreprise au Québec en vue de tester cette hypothèse. Plusieurs essais cliniques de Phase III sont en cours, dont un au Canada, pour évaluer l'efficacité du BCG contre les infections causées par le SRAS-CoV-2 (résultats attendus en 2021). Dans le passé, le BCG a été utilisé à large échelle au Canada, mais actuellement, les indications sont limitées aux individus à haut risque et aux communautés dans lesquelles se produisent des éclosions de tuberculose, ainsi que pour le traitement du cancer de la vessie. L'intérêt potentiel du BCG en tant que mesure intérimaire pour contrôler la COVID-19 fait l'objet de discussions intenses dans la communauté scientifique et cela pourrait être envisagé pour des populations vulnérables au Canada. Pour conclure, la vaccination avec le BCG devrait être placée sur l'agenda des organismes de recherche, des comités scientifiques consultatifs et des autorités de santé publique fédérale, provinciales et territoriales.

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Bacillus Calmette–Guérin strain differences as the basis for immunotherapies against bladder cancer

Cited by 22 publications

References 70 publications

Clinical and molecular insights into BCG immunotherapy for melanoma

Clinical and molecular insights into BCG immunotherapy for melanoma

Bacillus Calmette Guérin (BCG) activates lymphocyte to promote autophagy and apoptosis of gastric cancer MGC-803 cell

Can BCG be useful to mitigate the COVID-19 pandemic? A Canadian perspective

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