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Phototheranostics immunoconjugates to detect eliminate triple negative breast cancer cells

: Hussain, A.; Zeppernick, E.; Amoury, M.; Bauerschlag, D.O.; Maass, N.; Bräutigam, K.; Meinhold-Heerlein, I.; Fischer, R.; Barth, S.

Oncology research and treatment 39 (2016), Supplement 1, S.49
ISSN: 2296-5270
ISSN: 2296-5262
Deutscher Krebskongress <32, 2016, Berlin>
Fraunhofer IME ()

Triple-negative breast cancer (TNBC) is a very heterogeneous disease with a comparably poor prognosis. TNBC are classified as tumors that lack expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Consequently, TNBC patients do not benefit from currently available receptor-targeted therapies. Photoimmuno-theranostics (PIT) approach holds great promise for improving cancer prognosis and management. It combines a minimally invasive approach with a targeted therapy: Specific antibodies are linked to nontoxic photosensitizers that can be activated at the target cell using light producing cytotoxic reactive oxygen species that kill malignant cells by inducing cell apoptosis and/or necrosis.
Due to TNBC heterogeneity, it is unlikely that any single targeted therapy will be efficacious in all TNBC patients. To overcome this limitation, we have investigated the use of three PIT agents targeting the most common cell receptors found in TNBC. Using SNAP-tag technology specific antibody fragments that target epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCam) and chondroitin sulfate proteoglycan 4 (CSPG4) were conjugated with the highly potent photosensitizer, IRDye®700DX phthalocyanine dye. These PIT agents show powerful imaging properties and highly potent phototherapeutic activity, individually and in combination. In four different TNBC cell lines that express different levels of EGFR, EpCAM and CSPG4 receptors, combination of PIT-agents lead to reduced cell viability and increased apoptosis rates in our in-vitro model. Furthermore, this method has an excellent safety profile due to the non-toxic effect of free IR700 dye, even after irradiation.