Pharmaceutical Research

, Volume 34, Issue 4, pp 696–703 | Cite as

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

  • Dirk Bauerschlag
  • Ivo Meinhold-Heerlein
  • Nicolai Maass
  • Andreas Bleilevens
  • Karen Bräutigam
  • Wa’el Al Rawashdeh
  • Stefano Di Fiore
  • Anke Maria Haugg
  • Felix Gremse
  • Julia Steitz
  • Rainer Fischer
  • Elmar Stickeler
  • Stefan Barth
  • Ahmad Fawzi Hussain
Research Paper

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.

KEY WORDS

antibody theranostic conjugate molecular targeting ovarian cancer photodynamic therapy theranostics 

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

Notes

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.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Dirk Bauerschlag
    • 1
  • Ivo Meinhold-Heerlein
    • 2
  • Nicolai Maass
    • 1
  • Andreas Bleilevens
    • 2
  • Karen Bräutigam
    • 3
  • Wa’el Al Rawashdeh
    • 4
  • Stefano Di Fiore
    • 5
  • Anke Maria Haugg
    • 2
  • Felix Gremse
    • 4
  • Julia Steitz
    • 6
  • Rainer Fischer
    • 5
    • 7
  • Elmar Stickeler
    • 2
  • Stefan Barth
    • 8
    • 9
  • Ahmad Fawzi Hussain
    • 2
  1. 1.Department of Gynecology and ObstetricsUniversity Medical Center Schleswig-HolsteinKielGermany
  2. 2.Department of Gynecology and ObstetricsUniversity Hospital RWTH AachenAachenGermany
  3. 3.Department of Gynecology and ObstetricsUniversity Hospital Schleswig-HolsteinLübeckGermany
  4. 4.Department of Experimental Molecular ImagingRWTH Aachen UniversityAachenGermany
  5. 5.Fraunhofer Institute for Molecular Biology and Applied Ecology IMEAachenGermany
  6. 6.Institute for Laboratory Animal ScienceUniversity Hospital RWTH AachenAachenGermany
  7. 7.Institute of Molecular BiotechnologyRWTH Aachen UniversityAachenGermany
  8. 8.Department of Pharmaceutical Product DevelopmentFraunhofer Institute for Molecular Biology and Applied Ecology IMEAachenGermany
  9. 9.South African Research Chair in Cancer Biotechnology, Institute of Infectious Disease and Molecular Medicine (IDM), Department of Integrative Biomedical Sciences, Faculty of Health SciencesUniversity of Cape TownObservatorySouth Africa

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