A specific photoimmunotheranostics agent to detect and eliminate skin cancer cells expressing EGFR

• Published in: Journal of cancer research and clinical oncology Vol. 142; no. 5; pp. 1003 - 1011
• Main Authors: von Felbert, Verena, Bauerschlag, Dirk, Maass, Nicolai, Bräutigam, Karen, Meinhold-Heerlein, Ivo, Woitok, Mira, Barth, Stefan, Hussain, Ahmad Fawzi
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-05-2016; Springer Nature B.V
• Subjects: Cancer Research; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Epidermal growth factor; Flow Cytometry; Fluorescent Dyes - metabolism; Guanine - analogs & derivatives; Guanine - chemistry; Hematology; Humans; Immunotherapy; Indoles - metabolism; Internal Medicine; Medicine; Medicine & Public Health; Melanoma - drug therapy; Melanoma - metabolism; Melanoma - pathology; Microscopy, Confocal; Oncology; Organosilicon Compounds - metabolism; Original Article – Cancer Research; Photochemotherapy; Photosensitizing Agents - pharmacology; Protein expression; Receptor, Epidermal Growth Factor - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Single-Chain Antibodies - chemistry; Skin cancer; Skin Neoplasms - drug therapy; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Tumor Cells, Cultured; Photodynamic therapy; Photoimmunotheranostics; Malignant skin cancer; Targeted cancer therapy; Epidermal growth factor receptor
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-016-2122-7

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 EC
50
’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.