title: Detection and Specific Elimination of EGFR+Ovarian Cancer Cells Using a Near Infrared Photoimmunotheranostic Approach.
abstract: Targeted theranostics is an alternative strategy in cancer management that aims to improve cancer detection and treatment simultaneously. This approach combines potent therapeutic and diagnostic agents with the specificity of different cell receptor ligands in one product. The success of antibody drug conjugates (ADCs) in clinical practice has encouraged the development of antibody theranostics conjugates (ATCs). However, the generation of homogeneous and pharmaceutically-acceptable ATCs remains a major challenge. The aim of this study is to detect and eliminate ovarian cancer cells on-demand using an ATC directed to EGFR.
  
  
  
  An ATC with a defined drug-to-antibody ratio was generated by the site-directed conjugation of IRDye®700 to a self-labeling protein (SNAP-tag) fused to an EGFR-specific antibody fragment (scFv-425).
  
  
  
  In vitro and ex vivo imaging showed that the ATC based on scFv-425 is suitable for the highly specific detection of EGFR+ovarian cancer cell, human tissues and ascites samples. The construct was also able to eliminate EGFR+cells and human ascites cells with IC50values of 45-66 nM and 40-90 nM, respectively.
  
  
  
  Our experiments provide a framework to create a versatile technology platform for the development of ATCs for precise detection and treatment of ovarian cancer cells.
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, 24105, Kiel, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bauerschlag
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Ivo
authors.initials: I
authors.lastname: Meinhold-Heerlein
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, 24105, Kiel, Germany.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Maass
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bleilevens
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Bräutigam
authors.affiliation: Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany.
authors.forename: Wa'el
authors.initials: W
authors.lastname: Al Rawashdeh
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Fiore
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Anke Maria
authors.initials: AM
authors.lastname: Haugg
authors.affiliation: Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Gremse
authors.affiliation: Institute for Laboratory Animal Science, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Steitz
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.|Institute of Molecular Biotechnology, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Stickeler
authors.affiliation: Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.|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.forename: Stefan
authors.initials: S
authors.lastname: Barth
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany. ahmad.hussain@rwth-aachen.de.
authors.forename: Ahmad Fawzi
authors.initials: AF
authors.lastname: Hussain
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000494:pharmacology*; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D017646:Organosilicon Compounds / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010778:Photochemotherapy; D057127:Single-Chain Antibodies / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D000068936:Theranostic Nanomedicine
chemical_list: D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; C000623382:IRDye700DX N-hydroxysuccinimide ester; D018796:Immunoconjugates; D007135:Immunoglobulin Variable Region; D007211:Indoles; D017646:Organosilicon Compounds; D057127:Single-Chain Antibodies; C114035:scFv 425; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: antibody theranostic conjugate; molecular targeting; ovarian cancer; photodynamic therapy; theranostics