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Updated: Jun 23, 2025
A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity
Published on: July 12, 2018
GPC3-targeted CAR-M cells exhibit potent antitumor activity against hepatocellular carcinoma
Lili Guan1, Shanshan Wu1, Qinyao Zhu1
1Applied Biology Laboratory, College of Environmental and Safety Engineering, Shenyang University of Chemical Technology, Shenyang, 110142, China.
Abstract:
Chimeric antigen receptor (CAR)-modified macrophages are a promising treatment for solid tumor. So far the potential effects of CAR-M cell therapy have rarely been investigated in hepatocellular carcinoma (HCC). Glypican-3 (GPC3) is a biomarker for a variety of malignancies, including liver cancer, which is not expressed in most adult tissues. Thus, it is an ideal target for the treatment of HCC. In this study, we engineered mouse macrophage cells with CAR targeting GPC3 and explored its therapeutic potential in HCC. First, we generated a chimeric adenoviral vector (Ad5f35) delivering an anti-GPC3 CAR, Ad5f35-anti-GPC3-CAR, which using the CAR construct containing the scFv targeting GPC3 and CD3ζ intracellular domain. Phagocytosis and killing effect indicated that macrophages transduced with Ad5f35-anti-GPC3-CAR (GPC3 CAR-Ms) exhibited antigen-specific phagocytosis and tumor cell clearance in vitro, and GPC3 CAR-Ms showed significant tumor-killing effects and promoted expression of pro-inflammatory (M1) cytokines and chemokines. In 3D NACs-origami spheroid model of HCC, CAR-Ms were further demonstrated to have a significant tumor killing effect. Together, our study provides a new strategy for the treatment of HCC through CAR-M cells targeting GPC3, which provides a basis for the research and treatment of hepatocellular carcinoma.
Insights
Chimeric antigen receptor-modified macrophages (CAR-Ms) targeting Glypican-3 (GPC3) show significant potential for treating hepatocellular carcinoma (HCC). This study demonstrates GPC3 CAR-Ms effectively clear HCC cells in vitro and in 3D models, offering a novel therapeutic strategy.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Engineering
Background:
- Hepatocellular carcinoma (HCC) remains a significant health challenge with limited treatment options.
- Chimeric antigen receptor (CAR)-modified macrophages (CAR-Ms) represent a novel immunotherapy approach for solid tumors.
- Glypican-3 (GPC3) is a highly specific biomarker for HCC, making it an attractive therapeutic target.
Purpose of the Study:
- To engineer GPC3-specific CAR-M cells for potential HCC treatment.
- To evaluate the in vitro and in vivo efficacy of GPC3 CAR-Ms against HCC.
- To explore the therapeutic potential of targeting GPC3 in hepatocellular carcinoma.
Main Methods:
- Generation of an anti-GPC3 CAR construct using a chimeric adenoviral vector (Ad5f35).
- Transduction of mouse macrophage cells with the Ad5f35-anti-GPC3-CAR vector to create GPC3 CAR-Ms.
- Assessment of antigen-specific phagocytosis, tumor cell killing, and cytokine/chemokine expression in vitro.
- Evaluation of GPC3 CAR-Ms in a 3D spheroid model of HCC.
Main Results:
- GPC3 CAR-Ms demonstrated antigen-specific phagocytosis and significant tumor cell clearance in vitro.
- Transduced macrophages exhibited potent tumor-killing effects and promoted pro-inflammatory (M1) cytokine and chemokine expression.
- CAR-Ms showed significant tumor-killing efficacy in a 3D NACs-origami spheroid model of HCC.
Conclusions:
- GPC3-targeted CAR-M cell therapy is a promising new strategy for treating hepatocellular carcinoma.
- Engineered GPC3 CAR-Ms provide a basis for further research and development in HCC immunotherapy.
- This approach offers a targeted and potentially effective treatment modality for GPC3-positive HCC.
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