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, Ahmad Fawzi Hussain*

*Corresponding author for this work
15 Citations (Scopus)

Abstract

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 IC50 values 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%.

Original languageEnglish
JournalOncotarget
Volume7
Issue number34
Pages (from-to)54925-54936
Number of pages12
DOIs
Publication statusPublished - 2016

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