Allogeneic cetuximab-armed gamma delta T cells using antibody-cell conjugation technology for the treatment of EGFR-expressing solid tumors
Background Targeting epidermal growth factor receptor (EGFR) has become a strategic approach in cancer therapy, using various modalities including chimeric antigen receptor (CAR)-αβT cell therapies. Despite significant advancements in autologous CAR-αβT cell therapies in B-cell lymphoma, current cel...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2025-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/7/e010500.full |
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| author | Yi-Chiu Kuo Hao-Kang Li Tai-Sheng Wu Ying Ru Chia-Yun Lee Pei-Ju Leng Yi-Chun Hsieh Yun-Jung Chiang Zih-Fei Cheng Yan-Liang Lin Shih-Chia Hsiao Sai-Wen Tang |
| author_facet | Yi-Chiu Kuo Hao-Kang Li Tai-Sheng Wu Ying Ru Chia-Yun Lee Pei-Ju Leng Yi-Chun Hsieh Yun-Jung Chiang Zih-Fei Cheng Yan-Liang Lin Shih-Chia Hsiao Sai-Wen Tang |
| author_sort | Yi-Chiu Kuo |
| collection | DOAJ |
| description | Background Targeting epidermal growth factor receptor (EGFR) has become a strategic approach in cancer therapy, using various modalities including chimeric antigen receptor (CAR)-αβT cell therapies. Despite significant advancements in autologous CAR-αβT cell therapies in B-cell lymphoma, current cell therapies face challenges such as potential risks associated with genetic engineering, waiting time and high costs of autologous CAR-αβT cell therapies. Innovations in click chemistry and bioorthogonal chemistry have enabled the development of antibody-cell conjugation (ACC) technology, which links cancer-targeting antibodies to immune cells without genetic modifications, potentially providing a safer profile.Methods In this study, we introduce ACE2016, an innovative allogeneic cell therapy targeting EGFR. ACE2016 is generated by ACC technology to conjugate donor-derived γδ2 T cells with the EGFR-specific antibody cetuximab.Results Our preclinical studies demonstrate that ACE2016 exhibits superior cytotoxicity against various EGFR-expressing cancer cell lines and minimal cytotoxic effects on normal cells. Mechanistic studies revealed that ACE2016 enhances cytotoxicity through increased capacity towards EGFR-expressing cancer cells, enhanced levels of cytotoxic cytokines and recruitment of peripheral cytotoxic cells, reflecting significant tumor suppression and prolonged survival in ACE2016-treated groups without causing treatment-related toxicity in vivo.Conclusions These findings support the clinical potential of ACE2016 as an off-the-shelf γδ2 T-cell therapy for EGFR-expressing cancers, offering a combination of specificity, scalability, and safety in the development of solid tumor therapy. |
| format | Article |
| id | doaj-art-02833a99ff4f44eebc89c8d2be5c328e |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-02833a99ff4f44eebc89c8d2be5c328e2025-08-20T02:39:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-07-0113710.1136/jitc-2024-010500Allogeneic cetuximab-armed gamma delta T cells using antibody-cell conjugation technology for the treatment of EGFR-expressing solid tumorsYi-Chiu Kuo0Hao-Kang Li1Tai-Sheng Wu2Ying Ru3Chia-Yun Lee4Pei-Ju Leng5Yi-Chun Hsieh6Yun-Jung Chiang7Zih-Fei Cheng8Yan-Liang Lin9Shih-Chia Hsiao10Sai-Wen Tang11Acepodia Biotech Inc, Alameda, California, USAAcepodia Biotech Inc, Alameda, California, USAAcepodia Biotech Inc, Alameda, California, USAAcepodia Biotech Inc, Alameda, California, USAAcepodia Biotech Inc, Alameda, California, USAAcepodia Biotech Inc, Alameda, California, USAAcepodia Biotech Inc, Alameda, California, USAAcepodia Biotech Inc, Alameda, California, USAAcepodia Biotech Inc, Alameda, California, USAAcepodia Biotech Inc, Alameda, California, USAAcepodia Biotech Inc, Alameda, California, USAAcepodia Biotech Inc, Alameda, California, USABackground Targeting epidermal growth factor receptor (EGFR) has become a strategic approach in cancer therapy, using various modalities including chimeric antigen receptor (CAR)-αβT cell therapies. Despite significant advancements in autologous CAR-αβT cell therapies in B-cell lymphoma, current cell therapies face challenges such as potential risks associated with genetic engineering, waiting time and high costs of autologous CAR-αβT cell therapies. Innovations in click chemistry and bioorthogonal chemistry have enabled the development of antibody-cell conjugation (ACC) technology, which links cancer-targeting antibodies to immune cells without genetic modifications, potentially providing a safer profile.Methods In this study, we introduce ACE2016, an innovative allogeneic cell therapy targeting EGFR. ACE2016 is generated by ACC technology to conjugate donor-derived γδ2 T cells with the EGFR-specific antibody cetuximab.Results Our preclinical studies demonstrate that ACE2016 exhibits superior cytotoxicity against various EGFR-expressing cancer cell lines and minimal cytotoxic effects on normal cells. Mechanistic studies revealed that ACE2016 enhances cytotoxicity through increased capacity towards EGFR-expressing cancer cells, enhanced levels of cytotoxic cytokines and recruitment of peripheral cytotoxic cells, reflecting significant tumor suppression and prolonged survival in ACE2016-treated groups without causing treatment-related toxicity in vivo.Conclusions These findings support the clinical potential of ACE2016 as an off-the-shelf γδ2 T-cell therapy for EGFR-expressing cancers, offering a combination of specificity, scalability, and safety in the development of solid tumor therapy.https://jitc.bmj.com/content/13/7/e010500.full |
| spellingShingle | Yi-Chiu Kuo Hao-Kang Li Tai-Sheng Wu Ying Ru Chia-Yun Lee Pei-Ju Leng Yi-Chun Hsieh Yun-Jung Chiang Zih-Fei Cheng Yan-Liang Lin Shih-Chia Hsiao Sai-Wen Tang Allogeneic cetuximab-armed gamma delta T cells using antibody-cell conjugation technology for the treatment of EGFR-expressing solid tumors Journal for ImmunoTherapy of Cancer |
| title | Allogeneic cetuximab-armed gamma delta T cells using antibody-cell conjugation technology for the treatment of EGFR-expressing solid tumors |
| title_full | Allogeneic cetuximab-armed gamma delta T cells using antibody-cell conjugation technology for the treatment of EGFR-expressing solid tumors |
| title_fullStr | Allogeneic cetuximab-armed gamma delta T cells using antibody-cell conjugation technology for the treatment of EGFR-expressing solid tumors |
| title_full_unstemmed | Allogeneic cetuximab-armed gamma delta T cells using antibody-cell conjugation technology for the treatment of EGFR-expressing solid tumors |
| title_short | Allogeneic cetuximab-armed gamma delta T cells using antibody-cell conjugation technology for the treatment of EGFR-expressing solid tumors |
| title_sort | allogeneic cetuximab armed gamma delta t cells using antibody cell conjugation technology for the treatment of egfr expressing solid tumors |
| url | https://jitc.bmj.com/content/13/7/e010500.full |
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