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Fine Tuning Antibody Conjugation Methods using SNAP-tag Technology

[ Vol. 17 , Issue. 10 ]

Author(s):

Karinna Chouman, Mira Woitok, Radoslav Mladenov, Claudia Kessler, Elmar Weinhold, Gisela Hanz, Rainer Fischer, Ivo Meinhold-Heerlein, Andreas Bleilevens, Gerrit Gresch, Anka Maria Haugg, Felix Zeppernick, Dirk Bauerschlag, Nicolai Maass, Elmar Stickeler, Katharina Kolberg and Ahmad Fawzi Hussain*   Pages 1434 - 1440 ( 7 )

Abstract:


Background: Targeted imaging and therapy (theranostics) is a promising approach for the simultaneous improvement of cancer diagnosis, prognosis and management. Therapeutic and imaging reagents are coupled to tumor-targeting molecules such as antibodies, providing a basis for truly personalized medicine. However, the development of antibody–drug conjugates with acceptable pharmaceutical properties is a complex process and several parameters must be optimized, such as the controlled conjugation method and the drug-to-antibody ratio.

Objective: The major aim of this work is to address fundamental key challenges for the development of versatile technology platform for generating homogenous immunotheranostic reagent.

Method: We conjugated the theranostics reagent IRDye700dx to a recombinant antibody fusion protein containing a self-labeling protein (SNAP-tag) which provides a unique reaction site.

Results: The resulting conjugate was suitable for the imaging of cancer cells expressing the epidermal growth factor receptor and demonstrated potent phototherapeutic and imaging activities against them.

Conclusion: Here, we describe a simple, rapid and robust site-directed labeling method that can be used to generate homogeneous immunoconjugate with defined pharmacological properties.

Keywords:

Theranostics, SNAP-tag technology, site-directed labeling method, antibody drug conjugate, photodynamic therapy, IRDye700, EGFR.

Affiliation:

Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, Helmholtz-Institute for Biomedical Engineering, Pauwelsstrasse 20, 52074, Aachen, Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, Helmholtz-Institute for Biomedical Engineering, Pauwelsstrasse 20, 52074, Aachen, Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52056, Aachen, Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52056, Aachen, Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, 24105 Kiel, Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, 24105 Kiel, Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Department of Gynaecology and Obstetrics University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen

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