title: A specific photoimmunotheranostics agent to detect and eliminate skin cancer cells expressing EGFR.
abstract: OBJECTIVE
  The term "theranostics" represents a new paradigm in medicine especially for cancer treatment. This term was coined by Funkhouser in 2002 and defines a reagent that combines therapeutic and diagnostic properties. It is widely believed that theranostics agents will have considerable impact on healthcare before, during, and after disease by improving cancer prognosis and management simultaneously. Current theranostics approaches still rely on passive tumor targeting strategies, which have scattergun effects and tend to damage both neoplastic and non-neoplastic cells.
  
  
  METHODS
  Here we describe a simple, controlled, and efficient method to generate homogeneous photoimmunotheranostics reagents. This method combines molecular optical imaging, photodynamic therapy, and immunotherapy using SNAP-tag technology. SNAP-tag is a derivative of the O(6)-alkylguanine-DNA alkyltransferase (AGT) which has the ability to efficiently conjugate to O(6)-benzylguanine (BG) molecules under physiological conditions depending on its folding pattern.
  
  
  RESULTS
  The theranostics agent was able to specifically recognize various epidermal growth factor receptor (EGFR)-expressing skin cancer cell lines using flow cytometry analysis and confocal microscopy and eliminate them at EC50's of 32-55 nM.
  
  
  CONCLUSIONS
  These experiments provide a framework for using SNAP-tag technology to generate homogeneous photoimmunotheranostics reagents with unified pharmacokinetic and therapeutic profiles. Furthermore, the reagent generated in this work could be used to simultaneously monitor and suppress the growth of skin squamous carcinoma and melanoma cells expressing EGFR.
authors: Department of Dermatology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors: Verena
authors: V
authors: von Felbert
authors: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, 24105, Kiel, Germany.
authors: Dirk
authors: D
authors: Bauerschlag
authors: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, 24105, Kiel, Germany.
authors: Nicolai
authors: N
authors: Maass
authors: Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
authors: Karen
authors: K
authors: Bräutigam
authors: Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors: Ivo
authors: I
authors: Meinhold-Heerlein
authors: Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
authors: Mira
authors: M
authors: Woitok
authors: South African Research Chair in Cancer Biotechnology, Institute of Infectious Disease and Molecular Medicine (IDM), Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, South Africa.
authors: Stefan
authors: S
authors: Barth
authors: Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany. ahmad.hussain@rwth-aachen.de.
authors: Ahmad Fawzi
authors: AF
authors: Hussain
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D007167:Immunotherapy; D007211:Indoles / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal; D017646:Organosilicon Compounds / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000737:chemistry; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D005456:Fluorescent Dyes; C000593031:IR700DX-mbc94; D007211:Indoles; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; C114035:scFv 425; C064976:O(6)-benzylguanine; D006147:Guanine; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor; Malignant skin cancer; Photodynamic therapy; Photoimmunotheranostics; Targeted cancer therapy