Potentiating Antibody-Dependent Cellular Cytotoxicity in Triple-Negative Breast Cancer via the Humanized Anti-CD147 Antibody

  • Antibodies (Basel). 2025 Apr 11;14(2):36. doi: 10.3390/antib14020036.
Kanyarat Thongheang  1  2 ,  Thanathat Pamonsupornwichit  2 ,  Kanokporn Sornsuwan  2  3 ,  On-Anong Juntit  2  3 ,  Tawan Chokepaichitkool  4 ,  Weeraya Thongkum  2  3  5 ,  Umpa Yasamut  1  2  5 ,  Chatchai Tayapiwatana  1  2  5
Affiliations
  • 1. Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
  • 2. Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
  • 3. Office of Research Administration, Chiang Mai University, Chiang Mai 50200, Thailand.
  • 4. Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
  • 5. Center of Innovative Immunodiagnostic Development, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
PMID: 40265417 DOI: 10.3390/antib14020036
Abstract

Background: Triple-negative breast Cancer (TNBC) is an aggressive subtype with high metastatic potential, poor prognosis, and the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). The lack of these receptors limits the standard treatments, such as hormone therapies and HER2-targeted antibodies like trastuzumab. These challenges highlight the critical need for novel therapeutic strategies. CD147, a Transmembrane Glycoprotein overexpressed in TNBC, promotes tumor progression, metastasis, and chemoresistance, making it a promising therapeutic target. This study evaluates the antibody-dependent cellular cytotoxicity (ADCC) of HuM6-1B9, a humanized anti-CD147 antibody, against MDA-MB-231 cells, a TNBC model.

Methods: CFSE-labelled MDA-MB-231 cells were co-cultured with PBMCs as effector cells (E:T ratio 80:1) in the presence of HuM6-1B9 and incubated for 4 h. Cells were then collected and stained with PI, and CFSE+/PI+ dead target cells were analyzed by flow cytometry.

Results: Co-culturing MDA-MB-231 cells with peripheral blood mononuclear cells (PBMCs) in the presence of HuM6-1B9 demonstrated effective ADCC induction without direct cytotoxicity. HuM6-1B9 induced 54.01% Cancer cell death via ADCC, significantly outperforming trastuzumab (26.14%) while sparing PBMCs.

Conclusion: These findings support HuM6-1B9 as a prospective TNBC therapeutic and warrant further investigation into its clinical potential.

Keywords
ADCC; CD147; antibody therapy; humanized antibody; triple-negative breast cancer.
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