bcg immunotherapy
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2021 ◽  
Vol 8 ◽  
Author(s):  
Zheng Liu ◽  
Gongwei Long ◽  
Yucong Zhang ◽  
Guoliang Sun ◽  
Wei Ouyang ◽  
...  

Background: Thulium laser resection of bladder tumors (TmLRBT) is recently considered as a common treatment option for non-muscle-invasive bladder cancers (NMIBC), but whether it is superior to Transurethral resection of bladder tumors (TURBT) are still undetermined.Materials and Methods: We retrospectively screened our institution database to identify patients who were treated by conventional TURBT or TmLRBT for NMIBC and followed by intravesical bacillus Calmette-Guérin (BCG) immunotherapy. The preoperative characteristics, perioperative outcomes, and recurrence-free survival were compared to assess the safety and efficacy of the two procedures.Results: Eventually, 90 patients who underwent TmLRBT (n = 37) or TURBT (n = 53) followed by intravesical BCG immunotherapy were included. Two groups were similar in baseline characteristics except for the smaller tumor size of the TmLRBT group(1.7 cm vs. 2.2 cm; P = 0.036). Obturator nerve reflex occurred in eight patients in the TURBT group and 3 of them suffered from bladder perforation while none happened in the TmLRBT group. The TmLRBT also had a shorter irrigation duration. In the multivariate Cox regression, the TmLRBT was related to less recurrence risk (HR: 0.268; 95% CI, 0.095–0.759; P = 0.013).Conclusion: Our results suggested that TmLRBT is safer than conventional TURBT with fewer perioperative complications, and it offers better cancer control, therefore might be a superior option for NMIBC patients with intermediate and high recurrence risk.


Author(s):  
Michael Harvey ◽  
Bodie Chislett ◽  
Marlon Perera ◽  
Nathan Lawrentschuk ◽  
Damien Bolton ◽  
...  
Keyword(s):  

2021 ◽  
Author(s):  
José Daniel Subiela ◽  
Óscar Rodríguez Faba ◽  
Júlia Aumatell ◽  
Julio Calderón ◽  
Asier Mercadé ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nina M. G. P. de Queiroz ◽  
Fabio V. Marinho ◽  
Ana Carolina V. S. C. de Araujo ◽  
Julia S. Fahel ◽  
Sergio C. Oliveira

AbstractBacillus Calmette-Guerin (BCG) is the only FDA approved first line therapy for patients with nonmuscle invasive bladder cancer. The purpose of this study is to better understand the role of innate immune pathways involved in BCG immunotherapy against murine bladder tumor. We first characterized the immunological profile induced by the MB49 mouse urothelial carcinoma cell line. MB49 cells were not able to activate an inflammatory response (TNF-α, IL-6, CXCL-10 or IFN-β) after the stimulus with different agonists or BCG infection, unlike macrophages. Although MB49 cells are not able to induce an efficient immune response, BCG treatment could activate other cells in the tumor microenvironment (TME). We evaluated BCG intratumoral treatment in animals deficient for different innate immune molecules (STING−/−, cGAS−/−, TLR2−/−, TLR3−/−, TLR4−/−, TLR7−/−, TLR9−/−, TLR3/7/9−/−, MyD88−/−, IL-1R−/−, Caspase1/11−/−, Gasdermin-D−/− and IFNAR−/−) using the MB49 subcutaneous mouse model. Only MyD88−/− partially responded to BCG treatment compared to wild type (WT) mice, suggesting a role played by this adaptor molecule. Additionally, BCG intratumoral treatment regulates cellular infiltrate in TME with an increase of inflammatory macrophages, neutrophils and CD8+ T lymphocytes, suggesting an immune response activation that favors tumor remission in WT mice but not in MyD88−/−. The experiments using MB49 cells infected with BCG and co-cultured with macrophages also demonstrated that MyD88 is essential for an efficient immune response. Our data suggests that BCG immunotherapy depends partially on the MyD88-related innate immune pathway.


2021 ◽  
Vol 9 (7) ◽  
pp. e002707
Author(s):  
Erkko Ylösmäki ◽  
Manlio Fusciello ◽  
Beatriz Martins ◽  
Sara Feola ◽  
Firas Hamdan ◽  
...  

BackgroundIntratumoral BCG therapy, one of the earliest immunotherapies, can lead to infiltration of immune cells into a treated tumor. However, an increase in the number of BCG-induced tumor-specific T cells in the tumor microenvironment could lead to enhanced therapeutic effects.MethodsHere, we have developed a novel cancer vaccine platform based on BCG that can broaden BCG-induced immune responses to include tumor antigens. By physically attaching tumor-specific peptides onto the mycobacterial outer membrane, we were able to induce strong systemic and intratumoral T cell-specific immune responses toward the attached tumor antigens. These therapeutic peptides can be efficiently attached to the mycobacterial outer membrane using a poly-lysine sequence N-terminally fused to the tumor-specific peptides.ResultsUsing two mouse models of melanoma and a mouse model of colorectal cancer, we observed that the antitumor immune responses of BCG could be improved by coating the BCG with tumor-specific peptides. In addition, by combining this novel cancer vaccine platform with anti-programmed death 1 (anti-PD-1) immune checkpoint inhibitor (ICI) therapy, the number of responders to anti-PD-1 immunotherapy was markedly increased.ConclusionsThis study shows that intratumoral BCG immunotherapy can be improved by coating the bacteria with modified tumor-specific peptides. In addition, this improved BCG immunotherapy can be combined with ICI therapy to obtain enhanced tumor growth control. These results warrant clinical testing of this novel cancer vaccine platform.


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