Detection and Specific Elimination of EGFR+ Ovarian Cancer Cells Using a Near Infrared Photoimmunotheranostic Approach
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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.
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).
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.
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 WORDSantibody theranostic conjugate molecular targeting ovarian cancer photodynamic therapy theranostics
Antibody drug conjugate
Antibody theranostic conjugate
Epidermal growth factor receptor
Single-chain variable fragment
Sentinel lymph nodes
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.
- 7.du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials. Cancer. 2009;115:1234–44.CrossRefPubMedGoogle Scholar
- 15.Amoury M, Bauerschlag D, Zeppernick F, von Felbert V, Berges N, Di Fiore S et al. Photoimmunotheranostic agents for triple-negative breast cancer diagnosis and therapy that can be activated on demand. Oncotarget. 2016; 54925–36.Google Scholar
- 19.Sharma SK, Pourat J, Carlin S, Abdel-Atti D, Bankovich A, Sisodiya V, et al. A DLL3-targeted theranostic for small cell lung cancer: Imaging a low density target with a site-specifically modified radioimmunoconjugate. J Nucl Med. 2016;57:50.Google Scholar
- 24.Tummers QR, Hoogstins CE, Gaarenstroom KN, de Kroon CD, van Poelgeest MI, Vuyk J et al. Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17. Oncotarget. 2016: 32144–55.Google Scholar
- 25.Tummers QR, Hoogstins CE, Peters AA, de Kroon CD, Trimbos JB, van de Velde CJ, et al. The value of intraoperative near-infrared fluorescence imaging based on enhanced permeability and retention of indocyanine green: feasibility and false-positives in ovarian cancer. PLoS One. 2015;10:e0129766.CrossRefPubMedPubMedCentralGoogle Scholar