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Detection and Specific Elimination of EGFR+ Ovarian Cancer Cells Using a Near Infrared Photoimmunotheranostic Approach

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Abstract

Purpose

Targeted theranostics is an alternative strategy in cancer management that aims to improve cancer detection and treatment simultaneously. This approach combines potent therapeutic and diagnostic agents with the specificity of different cell receptor ligands in one product. The success of antibody drug conjugates (ADCs) in clinical practice has encouraged the development of antibody theranostics conjugates (ATCs). However, the generation of homogeneous and pharmaceutically-acceptable ATCs remains a major challenge. The aim of this study is to detect and eliminate ovarian cancer cells on-demand using an ATC directed to EGFR.

Methods

An ATC with a defined drug-to-antibody ratio was generated by the site-directed conjugation of IRDye®700 to a self-labeling protein (SNAP-tag) fused to an EGFR-specific antibody fragment (scFv-425).

Results

In vitro and ex vivo imaging showed that the ATC based on scFv-425 is suitable for the highly specific detection of EGFR+ ovarian cancer cell, human tissues and ascites samples. The construct was also able to eliminate EGFR+ cells and human ascites cells with IC50 values of 45–66 nM and 40–90 nM, respectively.

Conclusion

Our experiments provide a framework to create a versatile technology platform for the development of ATCs for precise detection and treatment of ovarian cancer cells.

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Abbreviations

ADC:

Antibody drug conjugate

ATC:

Antibody theranostic conjugate

EGFR:

Epidermal growth factor receptor

FITC:

Fluorescein isothiocyanate

ICG:

Indocyanine green

NIR:

Near-infrared

scFv:

Single-chain variable fragment

SLN:

Sentinel lymph nodes

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to thank Dr. Richard M Twyman for editing the manuscript. The authors declare that they have no conflict of interest.

Author information

Author notes

    Authors and Affiliations

    1. Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, 24105, Kiel, Germany

      Dirk Bauerschlag & Nicolai Maass

    2. Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany

      Ivo Meinhold-Heerlein, Andreas Bleilevens, Anke Maria Haugg, Elmar Stickeler & Ahmad Fawzi Hussain

    3. Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

      Karen Bräutigam

    4. Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany

      Wa’el Al Rawashdeh & Felix Gremse

    5. Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany

      Stefano Di Fiore & Rainer Fischer

    6. Institute for Laboratory Animal Science, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany

      Julia Steitz

    7. Institute of Molecular Biotechnology, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany

      Rainer Fischer

    8. Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany

      Stefan Barth

    9. South African Research Chair in Cancer Biotechnology, Institute of Infectious Disease and Molecular Medicine (IDM), Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, South Africa

      Stefan Barth

    Authors
    1. Dirk Bauerschlag
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    Corresponding author

    Correspondence to Ahmad Fawzi Hussain.

    Additional information

    Dirk Bauerschlag and Ivo Meinhold-Heerlein contributed equally to this work.

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    Bauerschlag, D., Meinhold-Heerlein, I., Maass, N. et al. Detection and Specific Elimination of EGFR+ Ovarian Cancer Cells Using a Near Infrared Photoimmunotheranostic Approach. Pharm Res 34, 696–703 (2017). https://doi.org/10.1007/s11095-017-2096-4

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    • DOI: https://doi.org/10.1007/s11095-017-2096-4

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