PNFLBA-12 TARGETING EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) AND HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 EXPRESSING BLADDER CANCER USING COMBINATION PHOTOIMMUNOTHERAPY (PIT)

Abstract

You have accessJournal of UrologyPlenary: Next Frontier (PNFLBA)1 Apr 2017PNFLBA-12 TARGETING EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) AND HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 EXPRESSING BLADDER CANCER USING COMBINATION PHOTOIMMUNOTHERAPY (PIT) mohammad siddiqui, Reema Railkar, Thomas Sanford, Peter Choyke, Hisataka Kobayashi, and Piyush Agarwal mohammad siddiquimohammad siddiqui More articles by this author , Reema RailkarReema Railkar More articles by this author , Thomas SanfordThomas Sanford More articles by this author , Peter ChoykePeter Choyke More articles by this author , Hisataka KobayashiHisataka Kobayashi More articles by this author , and Piyush AgarwalPiyush Agarwal More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.03.038AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder cancer (BC) is heterogeneous, expressing various cell surface targets, such as EGFR and Her2. Photoimmunotherapy (PIT) involves antibodies (Abs) conjugated to a photoabsorber (PA), IR Dye 700Dx, and then activated by Near infra-red light (NIR) to specifically target tumors. Our lab has previously shown that tumors expressing high levels of EGFR can be efficiently targeted with PIT. However, PIT is less effective when a tumor lacks “overwhelming” expression of a single target. Here, we present a novel, combinatorial PIT approach for such tumors expressing EGFR and Her2, using Panitumumab-IR700 (PanIR700) and Trastuzumumab-IR700 (TraIR700) antibodies, respectively. METHODS BC cell lines were analyzed for expression of EGFR and Her2 using flow cytometery. Concurrent and optimal binding of both PA-labeled Abs were determined using flow cytometery. NIR LD50 of multiple treatment regimens were determined to analyze in vitro efficacy of combination PIT. RESULTS The SW780 and RT112 cell lines showed low to moderate expression of EGFR and Her2. The EGFR expression was 143 fold higher in SW780 and 83 fold higher in RT112 over the isotype control. The Her2 expression was 42 fold higher in SW780 and 27 fold higher in RT112 over the isotype control. Hence, the ratio of cell surface EGFR to Her2 expression in both cell lines was about 3:1. For SW780, NIR LD50 was 28.66 J/cm2 for the combination PIT compared to 71.55 J/cm2 for the PanIR700 alone therapy. The NIR LD50 for RT112 was 14.66 J/cm2 for the combination PIT, with LD50 for PanIR700 alone therapy indeterminate from insufficient cell death. In both cases, the LD50 for TraIR700 alone therapy could not be determined from lack of sufficient cell death. CONCLUSIONS PIT is a new targeted treatment for bladder cancer that can be effectively used either locally or for metastatic lesions accessible by the NIR light. We demonstrate a novel and promising approach to treating BC by selectively inducing cell death in BC cell lines with low to moderate expression of cell surface markers of EGFR and Her2 using combination PIT. This will be further evaluated in a xenograft model. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e915 Advertisement Copyright & Permissions© 2017MetricsAuthor Information mohammad siddiqui More articles by this author Reema Railkar More articles by this author Thomas Sanford More articles by this author Peter Choyke More articles by this author Hisataka Kobayashi More articles by this author Piyush Agarwal More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...