PD09-03 EXTRACELLULAR VESICLES: A MECHANISM OF ACTION OF BACILLUS CALMETTE-GUERIN AND A POTENTIAL BIOMARKER

Abstract

You have accessJournal of UrologyBladder Cancer: Non-invasive I (PD09)1 Sep 2021PD09-03 EXTRACELLULAR VESICLES: A MECHANISM OF ACTION OF BACILLUS CALMETTE-GUERIN AND A POTENTIAL BIOMARKER Carlos Ortiz-Bonilla, Scott Gerber, Hiroshi Miyamoto, Edith Lord, Edward Messing, and Yi-Fen Lee Carlos Ortiz-BonillaCarlos Ortiz-Bonilla More articles by this author , Scott GerberScott Gerber More articles by this author , Hiroshi MiyamotoHiroshi Miyamoto More articles by this author , Edith LordEdith Lord More articles by this author , Edward MessingEdward Messing More articles by this author , and Yi-Fen LeeYi-Fen Lee More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001977.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Extracellular vesicles (EVs), small double-membrane vesicles, have recently gained attention because of their potential roles in mediating immune responses and cancer treatments. Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy is arguably one of the most successful immunotherapies for cancer, yet a significant number of patients fail response to BCG, and its underlying mechanisms remain largely unknown. In this study, we aim to test a new mode of BCG action mediated by BCG immune-active EVs (EVsBCG) released by BC cells. METHODS: Two immuno-responsive BC cell lines, human T24 and murine MB49 were used. CFU of cultured Live TICE® BCG was determined and applied on in vitro and in vivo experiments. BCG-induced immuno-molecular alteration in BC cells and EVsBCG was determined by quantitative PCR, Western blotting and Nanoparticle Tracking Analysis. EVsBCG-activated immune responses in dendritic cells were assessed by flow cytometry analyses. Moreover, we examined whether priming mice with EVsBCG can enhance BCG efficacy using the MB49 syngeneic model. The profiles of urinary EVs from BCG patients were evaluated for their predictive value. RESULTS: In response to BCG treatment, T24 and MB49 BC cells showed a significant increase in EVs secretion. EVsBCG contain elevated levels of key proteins in modulating immune responses, including MHC-I, MHC-II and CD80, CD86 co-stimulatory molecules. EVsBCG activated dendritic cells in vitro. Most importantly, priming mice with EVsBCG enhances BCG immunotherapy efficacy as compared to naïve EVs-primed mice. Interestingly, patients who respond to BCG showed significantly increased urinary EV numbers after the third BCG instillation, compared to non-responders in a pilot project. CONCLUSIONS: A novel mode of BCG action was presented. We showed that BCG promotes the release of immuno-active EVs by BC cells. Those EVsBCG can directly activate dendritic cells to modulate BCG-induced anti-tumor host response that warrants the therapeutic benefit of EVsBCG as an adjuvant therapy. Together, these data suggest that BCEVs play an important role in the mechanism of action of BCG immunotherapy. More importantly, patient-derived EVs during BCG immunotherapy may serve as predictive biomarkers. Source of Funding: HOPE Foundation, GR500600 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e120-e120 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Carlos Ortiz-Bonilla More articles by this author Scott Gerber More articles by this author Hiroshi Miyamoto More articles by this author Edith Lord More articles by this author Edward Messing More articles by this author Yi-Fen Lee More articles by this author Expand All Advertisement Loading ...