Epidermal Growth Factor Receptor (EGFR) Targeted Photoimmunotherapy (PIT) for the Treatment of EGFR expressing Bladder Cancer
The use of light as a means of therapy for bladder cancer (BC) has a long history but has been hampered by a lack of tumor specificity and therefore, damage to the normal bladder mucosa. Here, we describe a targeted form of photo-therapy called photoimmunotherapy (PIT) which targets EGFR-expressing BC. Anti-EGFR antibody panitumumab (pan) was labeled with the photo-absorber (PA), IRDye 700Dx (IR700), to create a pan IR700 antibody-PA conjugate which is activated by near-infrared radiation (NIR). BC tissue microarray (TMA) and BC cell lines were analyzed for expression of EGFR. Mechanism of PIT induced cell death was studied using proliferation assays, transmission electron microscopy (TEM), and production of reactive oxygen species. Finally, the in vivo effect was studied in xenografts. EGFR staining of TMAs showed that while most BCs have expression of EGFR to a varying degree, squamous cell carcinomas (SCC) have the highest expression of EGFR. Pan IR700 activated by NIR light rapidly killed UMUC-5 cells, a bladder SCC line. Pan alone, pan IR700 without NIR, or NIR alone had no effect on cells. TEM demonstrated that cell death is due to necrosis. Singlet oxygen species contributed towards cell death. NIR-PIT with pan IR700 reduced growth compared to only pan IR700 treated UMUC-5 xenograft tumors. PIT is a new targeted treatment for bladder cancer. Pan IR700-induced PIT selectively kills EGFR-expressing BC cells in vitro and in vivo and therefore warrants further therapeutic studies in orthotopic xenografts of BC and ultimately in patients.
Molecular cancer therapeutics. 2017 Jun 15 [Epub ahead of print] Reema Railkar, L Spencer Krane, Q Quentin Li, Thomas Sanford, Mohammad Rashid Siddiqui, Diana Haines, Srinivas Vourganti, Sam J Brancato, Peter L Choyke, Hisataka Kobayashi, Piyush K Agarwal Urologic Oncology Branch, National Cancer Institute., Pathology/Histotechnology Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research., Department of Urology, Rush University Medical Center., Urology, University of Iowa., Molecular Imaging Program, Center for Cancer Research, National Cancer Institute., Urologic Oncology Branch, National Cancer Institute Read an Expert Commentary by the Author, Piyush Kumar Agarwal, MD