Fine Tuning Antibody Conjugation Methods using SNAP-tag Technology
| Autor: | Gisela Maria Hanz, Felix Zeppernick, Ivo Meinhold-Heerlein, Elmar Stickeler, Rainer Fischer, Ahmad Fawzi Hussain, Gerrit Gresch, Katharina Kolberg, Andreas Bleilevens, Claudia Kessler, Dirk Bauerschlag, Anka Maria Haugg, Elmar Weinhold, Karinna Chouman, Nicolai Maass, Radoslav Mladenov, Mira Woitok |
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| Přispěvatelé: | Publica |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Antibody-drug conjugate Indoles Computational biology Antibodies Theranostic Nanomedicine Structure-Activity Relationship 03 medical and health sciences Neoplasms Humans Organosilicon Compounds Epidermal growth factor receptor Pharmacology Dose-Response Relationship Drug Molecular Structure biology Chemistry business.industry Fusion protein Immunoconjugate ErbB Receptors SNAP-tag 030104 developmental biology Photochemotherapy Reagent biology.protein Molecular Medicine Personalized medicine business Conjugate |
| Zdroj: | Anti-Cancer Agents in Medicinal Chemistry. 17 |
| ISSN: | 1871-5206 |
| DOI: | 10.2174/1871520617666170213123737 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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