Research Papers:

Photoimmunotheranostic agents for triple-negative breast cancer diagnosis and therapy that can be activated on demand

Manal Amoury, Dirk Bauerschlag, Felix Zeppernick, Verena von Felbert, Nina Berges, Stefano Di Fiore, Isabell Mintert, Andreas Bleilevens, Nicolai Maass, Karen Bräutigam, Ivo Meinhold-Heerlein, Elmar Stickeler, Stefan Barth, Rainer Fischer and Ahmad Fawzi Hussain _

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Oncotarget. 2016; 7:54925-54936. https://doi.org/10.18632/oncotarget.10705

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Manal Amoury1,*, Dirk Bauerschlag2,*, Felix Zeppernick3, Verena von Felbert4, Nina Berges1, Stefano Di Fiore5, Isabell Mintert3, Andreas Bleilevens6, Nicolai Maass2, Karen Bräutigam7, Ivo Meinhold-Heerlein3, Elmar Stickeler3, Stefan Barth8,9,*, Rainer Fischer5,10,*, Ahmad Fawzi Hussain3,*

1Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, Helmholtz-Institute for Biomedical Engineering, 52074 Aachen, Germany

2Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany

3Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, 52074 Aachen, Germany

4Department of Dermatology, University Hospital RWTH Aachen, 52074 Aachen, Germany

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

6Department of Nuclear Medicine, University Hospital RWTH Aachen, 52074 Aachen, Germany

7Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, 23538 Lübeck, Germany

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

9Current address: Institute of Infectious Disease and Molecular Medicine (IDM), Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa

10Institute of Molecular Biotechnology, RWTH Aachen University, 52074 Aachen, Germany

*These authors contributed equally to this work

Correspondence to:

Ahmad Fawzi Hussain, email: [email protected]

Keywords: breast cancer, theranostics, photodynamic therapy, molecular targeting, antibody-based therapy

Received: April 20, 2016     Accepted: May 29, 2016     Published: July 19, 2016


Triple-negative breast cancer (TNBC) is a heterogeneous disease in which the tumors do not express estrogen receptor (ER), progesterone receptor (PgR) or human epidermal growth factor receptor 2 (HER2). Classical receptor-targeted therapies such as tamoxifen or trastuzumab are therefore unsuitable and combinations of surgery, chemotherapy and/or radiotherapy are required. Photoimmunotheranostics is a minimally invasive approach in which antibodies deliver nontoxic photosensitizers that emit light to facilitate diagnosis and produce cytotoxic reactive oxygen species to induce apoptosis and/or necrosis in cancer cells. We developed a panel of photoimmunotheranostic agents against three TNBC-associated cell surface antigens. Antibodies against epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM) and chondroitin sulfate proteoglycan 4 (CSPG4) were conjugated to the highly potent near-infrared imaging agent/photosensitizer IRDye®700DX phthalocyanine using SNAP-tag technology achieving clear imaging in both breast cancer cell lines and human biopsies and highly potent phototherapeutic activity with IC50values of 62–165 nM against five different cell lines expressing different levels of EGFR, EpCAM and CSPG4. A combination of all three reagents increased the therapeutic activity against TNBC cells by up to 40%.

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