In vitro evidence of human immune responsiveness shows the improved potential of a recombinant BCG strain for bladder cancer treatment

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dc.contributorLab. Desenvolvimento de Vacinaspt_BR
dc.contributor.authorRodríguez, Duniapt_BR
dc.contributor.authorGoulart, Cibellypt_BR
dc.contributor.authorPagliarone, Ana Carolinapt_BR
dc.contributor.authorSilva, Eliane Pessoa dapt_BR
dc.contributor.authorCunegundes, Priscila Silvapt_BR
dc.contributor.authorNascimento, Ivan Pereirapt_BR
dc.contributor.authorBorra, Ricardo C.pt_BR
dc.contributor.authorDias, Waldely de Oliveirapt_BR
dc.contributor.authorTagliabue, Aldopt_BR
dc.contributor.authorBoraschi, Dianapt_BR
dc.contributor.authorLeite, Luciana Cezar de Cerqueirapt_BR
dc.date.accessioned2020-07-09T21:24:31Z-
dc.date.available2020-07-09T21:24:31Z-
dc.date.issued2019pt_BR
dc.identifier.citationRodríguez D, Goulart C, Pagliarone AC, Silva EP, Cunegundes PS, Nascimento IP, et al. In vitro evidence of human immune responsiveness shows the improved potential of a recombinant BCG strain for bladder cancer treatment. Front. immunol.. 2019 June;10:1460. doi:10.3389/fimmu.2019.01460.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/2789-
dc.description.abstractThe live attenuated mycobacterial strain BCG, in use as vaccine against tuberculosis, is considered the gold standard for primary therapy of carcinoma in situ of the bladder. Despite its limitations, to date it has not been surpassed by any other treatment. Our group has developed a recombinant BCG strain expressing the detoxified S1 pertussis toxin (rBCG-S1PT) that proved more effective than wild type BCG (WT-BCG) in increasing survival time in an experimental mouse model of bladder cancer, due to the well-known adjuvant properties of pertussis toxin. Here, we investigated the capacity of rBCG-S1PT to stimulate human immune responses, in comparison to WT-BCG, using an in vitro stimulation assay based on human whole blood cells that allows for a comprehensive evaluation of leukocyte activation. Blood leukocytes stimulated with rBCG-S1PT produced increased levels of IL-6, IL-8, and IL-10 as compared to WT-BCG, but comparable levels of IL-1ß, IL-2, IFN-?, and TNF-a. Stimulation of blood cells with the recombinant BCG strain also enhanced the expression of CD25 and CD69 on human CD4+ T cells. PBMC stimulated with rBCG-S1PT induced higher cytotoxicity to MB49 bladder cancer cells than WT-BCG-stimulated PBMC. These results suggest that the rBCG-S1PT strain is able to activate an immune response in human leukocytes that is higher than that induced by WT-BCG for parameters linked to better prognosis in bladder cancer (regulation of immune and early inflammatory responses), while fully comparable to WT-BCG for classical inflammatory parameters. This establishes rBCG-S1PT as a new highly effective candidate as immunotherapeutic agent against bladder cancer.pt_BR
dc.description.sponsorship(BNDES) Banco Nacional de Desenvolvimento Econômico e Socialpt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.format.extent1460pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofFrontiers in Immunologypt_BR
dc.rightsOpen accesspt_BR
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/pt_BR
dc.titleIn vitro evidence of human immune responsiveness shows the improved potential of a recombinant BCG strain for bladder cancer treatmentpt_BR
dc.typeArticlept_BR
dc.rights.licenseCC BYpt_BR
dc.identifier.doi10.3389/fimmu.2019.01460pt_BR
dc.identifier.urlhttps://doi.org/10.3389/fimmu.2019.01460pt_BR
dc.contributor.external(UFSCar) Universidade Federal de São Carlospt_BR
dc.contributor.externalConsiglio Nazionale delle Ricerche¦¦Italypt_BR
dc.identifier.citationvolume10pt_BR
dc.subject.keywordrecombinant BCGpt_BR
dc.subject.keywordbladder cancerpt_BR
dc.subject.keywordhuman immune cellspt_BR
dc.subject.keywordimmunotherapypt_BR
dc.subject.keywordadjuvantpt_BR
dc.subject.keywordCD4 T cellspt_BR
dc.subject.keywordcytokinespt_BR
dc.relation.ispartofabbreviatedFront immunolpt_BR
dc.identifier.citationabntv. 10, p. 1460, jun. 2019pt_BR
dc.identifier.citationvancouver2019 June;10:1460pt_BR
dc.contributor.butantanRodríguez, Dunia Del Carmen|:Pesquisador|:Laboratório de Desenvolvimento de Vacinas|:PrimeiroAutorpt_BR
dc.contributor.butantanGoulart, Cibelly|:Aluno|:Laboratório de Desenvolvimento de Vacinas|:pt_BR
dc.contributor.butantanPagliarone, Ana Carolina|:Colaborador|:Laboratório de Desenvolvimento de Vacinas|:pt_BR
dc.contributor.butantanSilva, Eliane Pessoa da|:Aluno|:Laboratório de Desenvolvimento de Vacinas|:pt_BR
dc.contributor.butantanCunegundes, Priscila Silva|:Aluno|:Laboratório de Desenvolvimento de Vacinas|:pt_BR
dc.contributor.butantanNascimento, Ivan Pereira|:Pesquisador|:Laboratório de Desenvolvimento de Vacinas|:pt_BR
dc.contributor.butantanDias, Waldely de Oliveira|:Pesquisador|:Laboratório de Desenvolvimento de Vacinas|:pt_BR
dc.contributor.butantanLeite, Luciana Cezar de Cerqueira|:Pesquisador|:Laboratório de Desenvolvimento de Vacinas|:Autor de correspondênciapt_BR
dc.sponsorship.butantanBanco Nacional de Desenvolvimento Econômico e Social (BNDES)¦¦11.2.0322.1pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦17/24832-6pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
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