You have accessJournal of UrologyCME1 Apr 2023PD04-08 BALIXAFORTIDE, A CXCR4 INHIBITOR, SYNERGIZES WITH DOCETAXEL TO DIMINISH TUMOR GROWTH IN A PROSTATE CANCER MODEL OF BONE METASTASIS Tyler Robinson, June Escara-Wilke, Jinlu Dai, Ann Arbor, MI, Russell Taichman, Johann Zimmermann, Allschwil Switzerland, and Evan Keller Tyler RobinsonTyler Robinson More articles by this author , June Escara-WilkeJune Escara-Wilke More articles by this author , Jinlu DaiJinlu Dai More articles by this author , Ann ArborAnn Arbor More articles by this author , MI MI More articles by this author , Russell TaichmanRussell Taichman More articles by this author , Johann ZimmermannJohann Zimmermann More articles by this author , Allschwil SwitzerlandAllschwil Switzerland More articles by this author , and Evan KellerEvan Keller More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003228.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) bone metastases have been shown to be more resistant to docetaxel than soft tissue metastases. The proinflammatory chemokine receptor CXCR4 has been shown to confer resistance to docetaxel (DOC) in PCa cells. Balixafortide (BLX) is an epitope mimetic inhibitor of CXCR4. Accordingly, we hypothesized and evaluated if BLX would enhance docetaxel-mediated antitumor activity in PCa bone metastases. METHODS: PC-3 luciferase-labeled cells were injected into the tibia of mice to model bone metastases. Four treatment groups were created: vehicle (1% DMSO in DPBS), DOC (5mg/kg), BLX (20mg/kg), and Combo (receiving both DOC and BLX). Mice were injected twice daily subcutaneously with either vehicle or BAL starting on day 1 and weekly intraperitoneally with DOC starting on day one. Tumor burden was measured weekly via bioluminescent imaging. At end of study (29 days), radiographs were taken of the tibiae and blood was collected. Serum levels of TRAcP, IL2, and IFNγ levels were measured using ELISA. Harvested tibiae were decalcified and stained for Ki67, cleaved caspase-3, and CD34 positive cells or microvessels were quantified. Statistical analysis was performed using ANOVA or Student’s t-test. RESULTS: Tumor burden was lower in the Combo group compared to the individual treatment groups. The Combo group had fewer mice with large bone lesions and the lowest TRAcP levels compared to the other groups. No significant difference in Ki67 staining was found among the groups; whereas, cleaved caspase-3 staining was lowest in the Combo group and highest in the BLX. The DOC and Combo groups had more CD34+ microvessels than the control and BLX groups. There was no difference between the treatment groups for IL-2, but the Combo group had increased levels of IFNγ compared to other groups. CONCLUSIONS: Our data demonstrate that that a combination of BLX and DOC has greater anti-tumor activity in a model of PCa bone metastases than either drug alone. The anti-tumor activity was also associated with decreased tumor-induced bone lesions. The mechanism for the anti-tumor activity is not completely elucidated at this time but does not appear to be through impacting proliferation. The observation that IFNγ was increased in the Combo group compared to other groups suggests that immune cell activation contributes to the anti-tumor effect. These data support further evaluation of this combination in metastatic PCa. Source of Funding: This work was supported by Spexis Ltd © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e145 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tyler Robinson More articles by this author June Escara-Wilke More articles by this author Jinlu Dai More articles by this author Ann Arbor More articles by this author MI More articles by this author Russell Taichman More articles by this author Johann Zimmermann More articles by this author Allschwil Switzerland More articles by this author Evan Keller More articles by this author Expand All Advertisement PDF downloadLoading ...