MP98-09 SYNERGISTIC IMMUNO-PHOTOTHERMAL NANOTHERAPY (SYMPHONY): A NOVEL TREATMENT FOR LOCALIZED AND METASTATIC BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology V1 Apr 2017MP98-09 SYNERGISTIC IMMUNO-PHOTOTHERMAL NANOTHERAPY (SYMPHONY): A NOVEL TREATMENT FOR LOCALIZED AND METASTATIC BLADDER CANCER Steven C. Brousell, Yang Liu, Paolo F. Maccarini, Gregory M. Palmer, Wiguins Etienne, Yulin Zhao, Chen-Ting Lee, Tuan Vo-Dinh, and Brant A. Inman Steven C. BrousellSteven C. Brousell More articles by this author , Yang LiuYang Liu More articles by this author , Paolo F. MaccariniPaolo F. Maccarini More articles by this author , Gregory M. PalmerGregory M. Palmer More articles by this author , Wiguins EtienneWiguins Etienne More articles by this author , Yulin ZhaoYulin Zhao More articles by this author , Chen-Ting LeeChen-Ting Lee More articles by this author , Tuan Vo-DinhTuan Vo-Dinh More articles by this author , and Brant A. InmanBrant A. Inman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3074AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We developed a novel treatment for localized and metastatic bladder cancer comprised of gold nanoparticle-based photothermal therapy and immunotherapy (SYMPHONY). We demonstrate that it effectively ablates primary tumors, destroys metastases abscopally, and induces potent anti-tumor immunity. METHODS MB49 murine bladder cancer cells were injected into the bilateral flanks of C57BL/6 mice and grown until 100 mm3 in size. PEG-functionalized gold nanostars, developed and manufactured by our team, were administered intravenously. A 808-nm laser (0.6 W/cm2) was used to trigger plasmonic heat production from the gold nanostars in the left flank 24 hours after injection, while the contralateral flank was left untreated. Anti-PD-L1 antibody immunotherapy was co-administered intraperitoneally and repeated q3days. Mice were assessed for ipsilateral and contralateral tumor response and survival. Flow cytometry, multiplex cytokine profiling, and T cell receptor sequencing were used to characterize the immune response. Mice achieving a complete response were rechallenged with an additional injection of MB49 tumor cells 90 days later. RESULTS Gold nanostar-mediated phototherapy alone completely ablated ipsilateral tumors in 4/5 of mice (pT0 at necropsy) but contralateral tumors grew and all 5 mice required sacrifice within 14 days. Anti-PD-L1 therapy alone slowed tumor growth in 3/5 mice, but tumors rapidly began growing again and 5/5 mice required sacrifice by 45 days. Combined treatment (i.e. SYMPHONY) ablated 5/5 ipsilateral tumors and resulted in partial (3/5) and complete responses (2/5) of untreated contralateral tumors, demonstrating a strong abscopal effect. After 90 days of follow-up, the two mice achieving a complete response with SYMPHONY were rechallenged with MB49 and neither developed a tumor over the ensuing 4 weeks indicating strong and effective immune memory. Flow cytometry showed CD4 and CD8 T cell proliferation, decreased myeloid derived suppressor cells, and increased IL2 with SYMPHONY. CONCLUSIONS SYMPHONY treatment resulted not only in effective ablation of primary tumors but also in immune-mediated abscopal destruction of untreated distant tumors. Strong and permanent anti-tumor immunity developed in some mice, indicating that with further optimization, SYMPHONY may be able to cure more advanced bladder cancers. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1315 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Steven C. Brousell More articles by this author Yang Liu More articles by this author Paolo F. Maccarini More articles by this author Gregory M. Palmer More articles by this author Wiguins Etienne More articles by this author Yulin Zhao More articles by this author Chen-Ting Lee More articles by this author Tuan Vo-Dinh More articles by this author Brant A. Inman More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...