Fine Tuning Antibody Conjugation Methods using SNAP-tag Technology

Title:Fine Tuning Antibody Conjugation Methods using SNAP-tag Technology

Volume: 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*

Affiliation:

• Department of Gynaecology and Obstetrics University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen,Germany

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

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.

Cite this article as:

Chouman Karinna, Woitok Mira, Mladenov Radoslav, Kessler Claudia, Weinhold Elmar, Hanz Gisela, Fischer Rainer, Meinhold-Heerlein Ivo, Bleilevens Andreas, Gresch Gerrit, Haugg Maria Anka, Zeppernick Felix, Bauerschlag Dirk, Maass Nicolai, Stickeler Elmar, Kolberg Katharina and Hussain Fawzi Ahmad*, Fine Tuning Antibody Conjugation Methods using SNAP-tag Technology, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (10) . https://dx.doi.org/10.2174/1871520617666170213123737