Abstract

Bladder cancer (BC) is heterogeneous and expresses various cell surface targets. Photoimmunotherapy (PIT) involves monoclonal antibodies (MAbs) conjugated to a photoabsorber (PA), IR Dye 700Dx, and then activated by near infra-red light (NIR) to specifically target tumors. We have demonstrated that tumors expressing EGFR can be targeted with PIT. However, PIT may be less effective when a tumor lacks “overwhelming” expression of a single target such as EGFR. We present a combinatorial PIT approach for targeting BC expressing EGFR and HER2, using PA- labeled panitumumab (pan) and trastuzumab (tra), respectively. Human BC tissues and cell lines were analyzed for EGFR and HER2 expression. Efficacy of PA-labeled MAbs singly and in combination was analyzed. About 45% of BC tissues stain for both EGFR and HER2. In vitro, the combination of pan IR700 and tra IR700 with NIR was more efficacious than either agent alone. Tumor xenografts treated with combination PIT showed significant tumor growth retardation. Combination PIT is a promising approach for treating BC with low/moderate expression of surface receptors. In addition, given the molecular heterogeneity of bladder cancer, targeting more than one surface receptor may allow for more effective cell death across different bladder tumors.

Details

Title
Targeting Epidermal Growth Factor Receptor (EGFR) and Human Epidermal Growth Factor Receptor 2 (HER2) Expressing Bladder Cancer Using Combination Photoimmunotherapy (PIT)
Author
Siddiqui, Mohammad R 1 ; Railkar Reema 2 ; Sanford, Thomas 2 ; Crooks, Daniel R 2 ; Eckhaus Michael A 3 ; Haines, Diana 4 ; Choyke, Peter L 5 ; Kobayashi Hisataka 5   VIAFID ORCID Logo  ; Agarwal, Piyush K 2 

 Center for Cancer Research, National Cancer Institute, Urologic Oncology Branch, Bethesda, USA (GRID:grid.417768.b) (ISNI:0000 0004 0483 9129); Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507) 
 Center for Cancer Research, National Cancer Institute, Urologic Oncology Branch, Bethesda, USA (GRID:grid.417768.b) (ISNI:0000 0004 0483 9129) 
 Office of the Director, National Institutes of Health, Diagnostic and Research Services Branch, Bethesda, USA (GRID:grid.453125.4) 
 Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research, Pathology Section, Pathology/Histotechnology Laboratory, Frederick, USA (GRID:grid.418021.e) (ISNI:0000 0004 0535 8394) 
 Center for Cancer Research, National Cancer Institute, Molecular Imaging Program, Bethesda, USA (GRID:grid.417768.b) (ISNI:0000 0004 0483 9129) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2180984763
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.