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

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 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%.

• Authors: 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
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 34 Pg. 54925-54936 (Aug 23 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27448975 (Publication Type: Journal Article)

Chemical References

• CSPG4 protein, human
• Chondroitin Sulfate Proteoglycans
• Epithelial Cell Adhesion Molecule
• IRDye700DX N-hydroxysuccinimide ester
• Immunoconjugates
• Indoles
• Isoindoles
• Membrane Proteins
• Organosilicon Compounds
• Photosensitizing Agents
• Recombinant Fusion Proteins
• Single-Chain Antibodies
• O(6)-benzylguanine
• Guanine
• ErbB Receptors
• phthalocyanine

Topics

• Cell Line, Tumor
• Cell Survival (drug effects, radiation effects)
• Chondroitin Sulfate Proteoglycans (immunology, metabolism)
• Epithelial Cell Adhesion Molecule (immunology, metabolism)
• ErbB Receptors (immunology, metabolism)
• Female
• Guanine (analogs & derivatives, chemistry)
• Humans
• Immunoconjugates (chemistry, therapeutic use)
• Indoles (chemistry, therapeutic use)
• Isoindoles
• Light
• MCF-7 Cells
• Membrane Proteins (immunology, metabolism)
• Microscopy, Confocal
• Organosilicon Compounds (chemistry, therapeutic use)
• Photochemotherapy (methods)
• Photosensitizing Agents (chemistry, therapeutic use)
• Recombinant Fusion Proteins (chemistry)
• Single-Chain Antibodies (chemistry, immunology)
• Triple Negative Breast Neoplasms (diagnosis, drug therapy, metabolism)