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

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, su...

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Main Authors: Kanyarat Thongheang, Thanathat Pamonsupornwichit, Kanokporn Sornsuwan, On-anong Juntit, Tawan Chokepaichitkool, Weeraya Thongkum, Umpa Yasamut, Chatchai Tayapiwatana
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Language:English
Published: MDPI AG 2025-04-01
Series:Antibodies
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Online Access:https://www.mdpi.com/2073-4468/14/2/36
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author Kanyarat Thongheang
Thanathat Pamonsupornwichit
Kanokporn Sornsuwan
On-anong Juntit
Tawan Chokepaichitkool
Weeraya Thongkum
Umpa Yasamut
Chatchai Tayapiwatana
author_facet Kanyarat Thongheang
Thanathat Pamonsupornwichit
Kanokporn Sornsuwan
On-anong Juntit
Tawan Chokepaichitkool
Weeraya Thongkum
Umpa Yasamut
Chatchai Tayapiwatana
author_sort Kanyarat Thongheang
collection DOAJ
description 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.
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institution Kabale University
issn 2073-4468
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publishDate 2025-04-01
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series Antibodies
spelling doaj-art-8b79ecbbd8ce4135972e77ab835fb2df2025-08-20T03:27:26ZengMDPI AGAntibodies2073-44682025-04-011423610.3390/antib14020036Potentiating Antibody-Dependent Cellular Cytotoxicity in Triple-Negative Breast Cancer via the Humanized Anti-CD147 AntibodyKanyarat Thongheang0Thanathat Pamonsupornwichit1Kanokporn Sornsuwan2On-anong Juntit3Tawan Chokepaichitkool4Weeraya Thongkum5Umpa Yasamut6Chatchai Tayapiwatana7Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandCenter of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandCenter of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandCenter of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandThailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandCenter of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandDivision of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandDivision of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandBackground: 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.https://www.mdpi.com/2073-4468/14/2/36triple-negative breast cancerCD147antibody therapyADCChumanized antibody
spellingShingle Kanyarat Thongheang
Thanathat Pamonsupornwichit
Kanokporn Sornsuwan
On-anong Juntit
Tawan Chokepaichitkool
Weeraya Thongkum
Umpa Yasamut
Chatchai Tayapiwatana
Potentiating Antibody-Dependent Cellular Cytotoxicity in Triple-Negative Breast Cancer via the Humanized Anti-CD147 Antibody
Antibodies
triple-negative breast cancer
CD147
antibody therapy
ADCC
humanized antibody
title Potentiating Antibody-Dependent Cellular Cytotoxicity in Triple-Negative Breast Cancer via the Humanized Anti-CD147 Antibody
title_full Potentiating Antibody-Dependent Cellular Cytotoxicity in Triple-Negative Breast Cancer via the Humanized Anti-CD147 Antibody
title_fullStr Potentiating Antibody-Dependent Cellular Cytotoxicity in Triple-Negative Breast Cancer via the Humanized Anti-CD147 Antibody
title_full_unstemmed Potentiating Antibody-Dependent Cellular Cytotoxicity in Triple-Negative Breast Cancer via the Humanized Anti-CD147 Antibody
title_short Potentiating Antibody-Dependent Cellular Cytotoxicity in Triple-Negative Breast Cancer via the Humanized Anti-CD147 Antibody
title_sort potentiating antibody dependent cellular cytotoxicity in triple negative breast cancer via the humanized anti cd147 antibody
topic triple-negative breast cancer
CD147
antibody therapy
ADCC
humanized antibody
url https://www.mdpi.com/2073-4468/14/2/36
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