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Updated: Feb 17, 2026

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
A Bispecific Antibody Based on Pertuzumab Fab Has Potent Antitumor Activity
Wentong Deng1,2, Jiayu Liu1,2, Haitao Pan1,2
1School of Pharmaceutical Sciences.
Abstract:
Human epidermal growth factor receptor 2 (HER2) is frequently overexpressed and activated in metastatic breast cancers. Monoclonal antibodies targeting Her2, such as trastuzumab and pertuzumab, have become important targeted therapies for patients with HER2-positive breast cancer. Both trastuzumab and pertuzumab can reduce Her2 positive tumor burden by inhibiting Her2 signaling and inducing ADCC activities (antibody dependent cell-mediated cytotoxicity). In this study, we have generated a bispecific antibody, Her2(Per)-S-Fab, by linking the pertuzumab Fab to an anti-CD16 single domain antibody. The Her2(Per)-S-Fab can be expressed and purified efficiently from Escherichia coli. In vitro and in vivo experiments showed Her2(Per)-S-Fab had potent cytotoxicity against Her2-positive tumor cells. Thus, Her2(Per)-S-Fab may provide an alternative to treat Her2-positive cancer patients.
Insights
A novel bispecific antibody, Her2(Per)-S-Fab, effectively targets and reduces HER2-positive breast cancer tumors. This antibody demonstrates potent cytotoxicity, offering a promising new treatment alternative for patients with HER2-positive cancers.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Human epidermal growth factor receptor 2 (HER2) overexpression drives metastatic breast cancer progression.
- Monoclonal antibodies like trastuzumab and pertuzumab are established HER2-targeted therapies, inhibiting HER2 signaling and mediating antibody-dependent cell-mediated cytotoxicity (ADCC).
Purpose of the Study:
- To develop and evaluate a novel bispecific antibody, Her2(Per)-S-Fab, for enhanced HER2-positive cancer treatment.
- To assess the efficacy of Her2(Per)-S-Fab in inhibiting tumor growth and mediating cytotoxicity.
Main Methods:
- Generation of a bispecific antibody (Her2(Per)-S-Fab) by conjugating a pertuzumab fragment (Fab) to an anti-CD16 single domain antibody.
- Efficient expression and purification of Her2(Per)-S-Fab using Escherichia coli.
- In vitro and in vivo studies to evaluate the cytotoxic effects of Her2(Per)-S-Fab against HER2-positive tumor cells.
Main Results:
- Her2(Per)-S-Fab was successfully expressed and purified from E. coli.
- Demonstrated potent in vitro and in vivo cytotoxicity against HER2-positive tumor cells.
- Indicated potential for enhanced anti-tumor activity compared to existing therapies.
Conclusions:
- Her2(Per)-S-Fab is a viable bispecific antibody candidate for targeting HER2-positive cancers.
- This novel antibody demonstrates significant anti-tumor efficacy, presenting a potential new therapeutic option.
- Further investigation into Her2(Per)-S-Fab could lead to improved treatment strategies for HER2-positive breast cancer patients.
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