MP14-10 ENHANCED ANTITUMOR EFFECT OF THE COMBINATION OF BACILLE CALMETTE-GUÉRIN AND AN IMMUNE CHECKPOINT INHIBITOR IN BLADDER CANCER-ON-A-CHIP

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP14-10 ENHANCED ANTITUMOR EFFECT OF THE COMBINATION OF BACILLE CALMETTE-GUÉRIN AND AN IMMUNE CHECKPOINT INHIBITOR IN BLADDER CANCER-ON-A-CHIP Se Young Choi, Jong Hyun Tae, Byung Hoon Chi, In Ho Chang, Tae-Hyoung Kim, Soon Chul Myung, Jung Hoon Kim, Jin Wook Kim, and Yong Seong Lee Se Young ChoiSe Young Choi More articles by this author , Jong Hyun TaeJong Hyun Tae More articles by this author , Byung Hoon ChiByung Hoon Chi More articles by this author , In Ho ChangIn Ho Chang More articles by this author , Tae-Hyoung KimTae-Hyoung Kim More articles by this author , Soon Chul MyungSoon Chul Myung More articles by this author , Jung Hoon KimJung Hoon Kim More articles by this author , Jin Wook KimJin Wook Kim More articles by this author , and Yong Seong LeeYong Seong Lee More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003234.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We upgraded preexisting bladder cancer-on-a-chip (BCOC) by adding T cells and evaluated the antitumor effect of a combination of intravesical Bacille Calmette-Guérin (BCG) and pembrolizumab. METHODS: We fabricated bioprinted BCOC with microfluids, incorporating HT1376, MRC-5, HUVEC, THP-1 and Jurkat cells. We evaluated the effector-to-target cytotoxicity, cytokine, and cell viability in 2D culture, live/dead assay, migration assay, and cytokine assay in BCOC. Additionally, we evaluated the antitumor efficacy of the combination of BCG and pembrolizumab in an orthotopic mouse model. RESULTS: The combination group showed the most effective reduction compared to the control in 2D culture (100.0±0.8% vs. 36.4±0.8%, p<0.001). In BCOC, cancer cell viabilities were decreased at 3 days in the BCG group (70.1±9.8%, p=0.013) and combination group (49.3±8.1%, p<0.001). The combination group showed the highest immune reaction in the cytokine assay (interferon-γ, p=0.045; interleukin-6, p=0.037) and migration assay (fold change 1.3±0.1, p<0.001), whereas in the in vivo model, it showed lower signal intensities from days 10 to 14 compared to that in the control group (p=0.031 and p=0.014, respectively). No significant weight changes were observed among the groups. CONCLUSIONS: We developed a 3D bioprinted BCOC via use of the monocytic THP-1 cells and Jurkat T cells to assess the efficacy of immunotherapy. The combination of BCG and pembrolizumab showed the best antitumor efficacy in BCOC and animal models. Source of Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2019R1C1C1005170 & NRF-2022R1A2C2008207) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e186 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Se Young Choi More articles by this author Jong Hyun Tae More articles by this author Byung Hoon Chi More articles by this author In Ho Chang More articles by this author Tae-Hyoung Kim More articles by this author Soon Chul Myung More articles by this author Jung Hoon Kim More articles by this author Jin Wook Kim More articles by this author Yong Seong Lee More articles by this author Expand All Advertisement PDF downloadLoading ...