EpCAM- and EGFR-Specific Antibody Drug Conjugates for Triple-Negative Breast Cancer Treatment

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 tar...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-05, Vol.23 (11), p.6122
Main Authors: Zhang, Chaoyu, Sheng, Wenjie, Al-Rawe, Marwah, Mohiuddin, T M, Niebert, Marcus, Zeppernick, Felix, Meihold-Heerlein, Ivo, Hussain, Ahmad Fawzi
Format: Article
Language:English
Subjects:
antibody drug conjugate
Apoptosis
Breast cancer
Cancer therapies
Cell adhesion
Cell adhesion molecules
Conjugates
Conjugation
Cytotoxicity
EGFR
Enzymes
EpCAM
Epidermal growth factor
Epidermal growth factor receptors
Epithelial cells
Epithelium
ErbB-2 protein
Estrogen receptors
Estrogens
Flow cytometry
Fluorescence microscopy
Growth factors
Internalization
Medical prognosis
Microscopy
Monoclonal antibodies
Progesterone
Proteins
SNAP-tag technology
triple-negative breast cancer
tumor targeting therapy
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23116122