PD42-12 DEVELOPMENT OF A FIRST-IN-CLASS HUMANIZED ANTIBODY TARGETING CXCL1 IN BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II (PD42)1 Sep 2021PD42-12 DEVELOPMENT OF A FIRST-IN-CLASS HUMANIZED ANTIBODY TARGETING CXCL1 IN BLADDER CANCER Kaoru Murakami, Yuka Sasaki, Hideki Furuya, and Charles Rosser MurakamiKaoru Murakami More articles by this author , SasakiYuka Sasaki FuruyaHideki Furuya RosserCharles View All Author Informationhttps://doi.org/10.1097/JU.0000000000002056.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Chemokine (C-X-C motif) ligand 1 (CXCL1) plays a crucial role in tumor initiation, promotion, progression bladder cancer (BCa) development. We previously demonstrated that can be promising therapeutic target both vitro vivo cancer. Herein, we developed first-in-class humanized neutralizing monoclonal antibody towards (NTC-001). This study is final step pre-clinical stage. In study, aimed evaluate efficacy safety the move into phase clinical trials near future. METHODS: mouse anti-human antibody, resulting 2 variants (NTC-001 NTC-003). First, evaluated characteristics NTC-001 NTC-003 antibodies western blotting (WB) enzyme-linked immunosorbent assay (ELISA). also binding affinity Octet. Second, cell proliferation angiogenesis using BCa line (T24) human umbilical vein endothelial (HUVEC), respectively. addition, examined 50% inhibitory concentration (IC50) lines (T24, 5637, 253J, 253J-BV, RT112, UMUC14). when used combination with gemcitabine or cisplatin for analysis. Lastly, pharmacokinetic (PK) profile plasma from animal strains (CD-1 NSG-SGM3) receiving single intravenous injection was ELISA. RESULTS: specifically bound WB significantly inhibited tube formation HUVEC. T24, (p<0.001). Interestingly, effect on correlated levels expression lines. Compared expression-low group (RT112 UMUC-14), expression-high 253J-BV) tended show low IC50. Synergistic observed (combination index<1) though not cisplatin. Finally, PK half-life 324 hours 18 CD-1 NSG-SGM3, CONCLUSIONS: could agent BCa. are going proceed complete our investigational new drug enabling studies small large animals. Source Funding: Nonagen Therapeutic Corporation provided © 2021 American Urological Association Education Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e729-e729 Advertisement Copyright Permissions© Inc.MetricsAuthor Information Expand Loading ...