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Detection and Specific Elimination of EGFR+ Ovarian Cancer Cells Using a Near Infrared Photoimmunotheranostic Approach.
Bauerschlag, Dirk; Meinhold-Heerlein, Ivo; Maass, Nicolai; Bleilevens, Andreas; Bräutigam, Karen; Al Rawashdeh, Wa'el; Di Fiore, Stefano; Haugg, Anke Maria; Gremse, Felix; Steitz, Julia; Fischer, Rainer; Stickeler, Elmar; Barth, Stefan; Hussain, Ahmad Fawzi.
Afiliação
  • Bauerschlag D; Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, 24105, Kiel, Germany.
  • Meinhold-Heerlein I; Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
  • Maass N; Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, 24105, Kiel, Germany.
  • Bleilevens A; Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
  • Bräutigam K; Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
  • Al Rawashdeh W; Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany.
  • Di Fiore S; Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
  • Haugg AM; Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
  • Gremse F; Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany.
  • Steitz J; Institute for Laboratory Animal Science, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
  • Fischer R; Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
  • Stickeler E; Institute of Molecular Biotechnology, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany.
  • Barth S; Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
  • Hussain AF; Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Pharm Res ; 34(4): 696-703, 2017 04.
Article em En | MEDLINE | ID: mdl-28074431
PURPOSE: 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. METHODS: 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). RESULTS: 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 IC50 values of 45-66 nM and 40-90 nM, respectively. CONCLUSION: 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Fotoquimioterapia / Apoptose / Imunoconjugados / Receptores ErbB Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Fotoquimioterapia / Apoptose / Imunoconjugados / Receptores ErbB Idioma: En Ano de publicação: 2017 Tipo de documento: Article