Abstract
Purpose
The term “theranostics” represents a new paradigm in medicine especially for cancer treatment. This term was coined by Funkhouser in 2002 and defines a reagent that combines therapeutic and diagnostic properties. It is widely believed that theranostics agents will have considerable impact on healthcare before, during, and after disease by improving cancer prognosis and management simultaneously. Current theranostics approaches still rely on passive tumor targeting strategies, which have scattergun effects and tend to damage both neoplastic and non-neoplastic cells.
Methods
Here we describe a simple, controlled, and efficient method to generate homogeneous photoimmunotheranostics reagents. This method combines molecular optical imaging, photodynamic therapy, and immunotherapy using SNAP-tag technology. SNAP-tag is a derivative of the O(6)-alkylguanine-DNA alkyltransferase (AGT) which has the ability to efficiently conjugate to O(6)-benzylguanine (BG) molecules under physiological conditions depending on its folding pattern.
Results
The theranostics agent was able to specifically recognize various epidermal growth factor receptor (EGFR)-expressing skin cancer cell lines using flow cytometry analysis and confocal microscopy and eliminate them at EC50’s of 32–55 nM.
Conclusions
These experiments provide a framework for using SNAP-tag technology to generate homogeneous photoimmunotheranostics reagents with unified pharmacokinetic and therapeutic profiles. Furthermore, the reagent generated in this work could be used to simultaneously monitor and suppress the growth of skin squamous carcinoma and melanoma cells expressing EGFR.
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Acknowledgments
The authors thank Dr. Stefano DiFiore from Fraunhofer IME and Nina Berges from Institute of Applied Medical Engineering for their support in confocal microscopy.
Authors’ contributions
V. V. and D. B. performed the experiments. A. F. H. and S. B. were responsible for project planning and discussing the results. V. V. and D. B. drafted the manuscript. A. F. H. and S.B. revised the manuscript.
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All the Authors declare that they have no conflict of interest.
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This article does not contain any studies with human participants or animals performed by any of the authors.
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Verena von Felbert, Dirk Bauerschlag, Stefan Barth and Ahmad Fawzi Hussain have equally contributed to this work.
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von Felbert, V., Bauerschlag, D., Maass, N. et al. A specific photoimmunotheranostics agent to detect and eliminate skin cancer cells expressing EGFR. J Cancer Res Clin Oncol 142, 1003–1011 (2016). https://doi.org/10.1007/s00432-016-2122-7
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DOI: https://doi.org/10.1007/s00432-016-2122-7