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• W3189074003 abstract "You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III (MP66)1 Sep 2021MP66-20 BLADDER CANCER EXTRACELLULAR VESICLES: A NOVEL ANTI-TUMOR VACCINE Carlos Ortiz-Bonilla, Taylor Ucello, Scott Gerber, Hiroshi Miyamoto, Edith Lord, Edward Messing, and Yi-Fen Lee Carlos Ortiz-BonillaCarlos Ortiz-Bonilla More articles by this author , Taylor UcelloTaylor Ucello 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.0000000000002106.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Extracellular vesicles (EV) comprise a diverse group of small vesicles secreted by almost all types of cells into the extracellular space. EV have been shown to play crucial roles in carrying and presenting functional MHC-peptide complexes to modulate antigen-specific CD8 T cell responses. However, the therapeutic potential and immunogenicity of EV-based vaccines has not yet tested. In this project, we aim to investigate the potential of using bladder cancer (BC) EV as a cancer vaccine in a pre-clinical model. METHODS: EV derived from murine MB49 BC cells were characterized by Nanoparticle Tracking Analysis, and EV cargo proteins and encapsulated cytokines were analyzed by Mass Spectrometry and pro-inflammatory cytokine array. The anti-tumor immunity of BCEV was evaluated in the MB49 syngeneic mouse model where mice were primed with MB49 EV prior MB49 tumors inoculation. Tumor growth was monitored and tumor-infiltrated immune cell populations were determined by flow cytometry. Anti-CD8 neutralizing antibody as well as IgG isotype control antibody were administrated to mice to test whether BCEV-mediated anti-tumor immunity is dependent on CD8 T cells. Moreover, we determined whether priming mice with MB49EV can prevent colonization of un-related colon MC-38 tumors in vivo. RESULTS: Proteomic and cytokine array analysis have revealed that MB49 EV encapsulated enriched immuno-active cargo proteins and cytokines with function linked to both innate and adaptive immune responses. To our surprise, priming mice with MB49 EV completely prevented MB49 tumor growth in vivo and neutralizing CD8 T cells abolished the MB49 EV-mediated anti-tumor effect. Interestingly, MB49 EV priming was unable to prevent MC-38 tumor growth but hindered significantly their growth in vivo. Flow cytometry analyses revealed increased levels of tumor-infiltrated granulocytes, inflammatory monocytes, and natural killer cells in EV-primed MC-38 tumors. In addition, those tumors also showed increased numbers of infiltrated antigen-presenting dendritic cells and antigen-specific CD4 and CD8 T cells. CONCLUSIONS: For the first time, we provided direct in vivo evidence that BCEV can prevent isogenic tumor growth, and such action is mainly mediated by CD8 T cells. They encapsulated enriched immunogenic cargo proteins and cytokines that could even promote anti-tumor host response against unrelated tumor growth. In summary, our study support the potential application of tumor-derived EV in personalized medicine, and open new avenue for developing therapeutic cancer vaccine based on patient-derived EV to prevent BC recurrence. Source of Funding: NCI RO1 CA173986 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1137-e1137 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Carlos Ortiz-Bonilla More articles by this author Taylor Ucello 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 PDF downloadLoading ..." @default.
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• W3189074003 title "MP66-20 BLADDER CANCER EXTRACELLULAR VESICLES: A NOVEL ANTI-TUMOR VACCINE" @default.
• W3189074003 doi "https://doi.org/10.1097/ju.0000000000002106.20" @default.
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