Journal article

Publication year: 2022

Journal: International Journal of Molecular Sciences

Volume number: 23

Issue number: 11

ISSN: 1661-6596

eISSN: 1422-0067

Open access status: Gold

DOI Link: https://doi.org/10.3390/ijms23116122

Publisher: MDPI

Abstract: 
Triple-negative breast cancer (TNBC) is a group of heterogeneous and refractory breast cancers with the absence of estrogen receptor (ER), progesterone receptor (PgR) and epidermal growth factor receptor 2 (HER2). Over the past decade, antibody drug conjugates (ADCs) have ushered in a new era of targeting therapy. Since the epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM) are over expressed on triple-negative breast cancer, we developed novel ADCs by conjugating benzylguanine (BG)-modified monomethyl auristatin E (MMAE) to EpCAM- and EGFR-specific SNAP-tagged single chain antibody fragments (scFvs). Rapid and efficient conjugation was achieved by SNAP-tag technology. The binding and internalization properties of scFv-SNAP fusion proteins were confirmed by flow cytometry and fluorescence microscopy. The dose-dependent cytotoxicity was evaluated in cell lines expressing different levels of EGFR and EpCAM. Both ADCs showed specific cytotoxicity to EGFR or EpCAM positive cell lines via inducing apoptosis at a nanomolar concentration. Our study demonstrated that EGFR specific scFv-425-SNAP-BG-MMAE and EpCAM-specific scFv-EpCAM-SNAP-BG-MMAE could be promising ADCs for the treatment of TNBC.

Harvard Citation style: Zhang, C., Sheng, W., Al-Rawe, M., Mohiuddin, T., Niebert, M., Zeppernick, F., et al. (2022) EpCAM- and EGFR-Specific Antibody Drug Conjugates for Triple-Negative Breast Cancer Treatment, International Journal of Molecular Sciences, 23(11), Article 6122. https://doi.org/10.3390/ijms23116122

APA Citation style: Zhang, C., Sheng, W., Al-Rawe, M., Mohiuddin, T., Niebert, M., Zeppernick, F., Meihold-Heerlein, I., & Hussain, A. (2022). EpCAM- and EGFR-Specific Antibody Drug Conjugates for Triple-Negative Breast Cancer Treatment. International Journal of Molecular Sciences. 23(11), Article 6122. https://doi.org/10.3390/ijms23116122