Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer
Background Triple negative breast cancer (TNBC) is a subtype of breast cancers with poor prognosis and targeted drug therapies are limited. To develop novel and efficacious therapies for TNBC, we developed a bispecific antibody F7AK3 that recognizes both trophoblast cell surface antigen 2 (TROP2) an...
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BMJ Publishing Group
2021-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/10/e003468.full |
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| author | Jing Wang Lin Li Huicheng Liu Lili Bai Liu Huang Na Ning Yijia Li Xuejiao Dong Qiuyang Du Minghui Xia Yufei Chen Likun Zhao Yanhu Li Qingwu Meng Yaqi Duan Jie Ming Andy Qingan Yuan Xiang-Ping Yang |
| author_facet | Jing Wang Lin Li Huicheng Liu Lili Bai Liu Huang Na Ning Yijia Li Xuejiao Dong Qiuyang Du Minghui Xia Yufei Chen Likun Zhao Yanhu Li Qingwu Meng Yaqi Duan Jie Ming Andy Qingan Yuan Xiang-Ping Yang |
| author_sort | Jing Wang |
| collection | DOAJ |
| description | Background Triple negative breast cancer (TNBC) is a subtype of breast cancers with poor prognosis and targeted drug therapies are limited. To develop novel and efficacious therapies for TNBC, we developed a bispecific antibody F7AK3 that recognizes both trophoblast cell surface antigen 2 (TROP2) and CD3 and evaluated its antitumor activities both in vitro and in vivo.Methods The binding affinities of F7AK3 to the two targets, TROP2 and CD3, were evaluated by surface plasmon resonance. Binding of F7AK3 to TNBC cells and T cells were evaluated by flow cytometry. Immunofluorescent staining was performed to demonstrate the interactions between T cells with TNBC cells. The cytotoxicity of T cells against TNBC cell lines and primary tumor cells mediated by F7AK3 were determined in vitro. In vivo antitumor activity of F7AK3 was investigated in a xenograft TNBC tumor model, using immunodeficient mice that were reconstituted with human peripheral blood mononuclear cells.Results We demonstrated that F7AK3 binds specifically to human TROP2 and CD3 antigens, as well as TNBC cell lines and primary tumor cells. Human T cells can only be activated by F7AK3 in the presence of target tumor cells. F7AK3 recruits T cells to TROP2+ tumor cells in vitro and into tumor tissues in vivo. Antitumor growth activity of F7AK3 is observed in a xenograft TNBC tumor model.Conclusion This study showed the antitumor potential of an anti-TROP2xCD3 bispecific antibody F7AK3 to TNBC tumor cells both in vitro and in vivo. These data demonstrate that F7AK3 has the potential to treat TNBC patients, which warrants further preclinical and clinical evaluation of the F7AK3 in advanced or metastatic TNBC patients. |
| format | Article |
| id | doaj-art-496da0e943304287b5b4e49e748a142e |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-496da0e943304287b5b4e49e748a142e2025-08-20T01:53:10ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-10-0191010.1136/jitc-2021-003468Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancerJing Wang0Lin Li1Huicheng Liu2Lili Bai3Liu Huang4Na Ning5Yijia Li6Xuejiao Dong7Qiuyang Du8Minghui Xia9Yufei Chen10Likun Zhao11Yanhu Li12Qingwu Meng13Yaqi Duan14Jie Ming15Andy Qingan Yuan16Xiang-Ping Yang17Department of Immunology, School of Basic Medicine, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, ChinaRemeGen Co. Ltd, Shandong, ChinaDepartment of Immunology, School of Basic Medicine, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, ChinaExcyte Biopharma Ltd, Beijing, Haidian Dist, ChinaDepartment of Oncology, Tongji Hospital, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, ChinaDepartment of Immunology, School of Basic Medicine, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, ChinaExcyte Biopharma Ltd, Beijing, Haidian Dist, ChinaDepartment of Immunology, School of Basic Medicine, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, ChinaDepartment of Immunology, School of Basic Medicine, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, ChinaDepartment of Immunology, School of Basic Medicine, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, China1 Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, ChinaExcyte Biopharma Ltd, Beijing, Haidian Dist, ChinaExcyte Biopharma Ltd, Beijing, Haidian Dist, ChinaExcyte Biopharma Ltd, Beijing, Haidian Dist, ChinaDepartment of Pathology, School of Basic Medicine, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, ChinaDepartment of Breast and Thyroid Surgery, Wuhan Union Hospital, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, ChinaExcyte Biopharma Ltd, Beijing, Haidian Dist, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaBackground Triple negative breast cancer (TNBC) is a subtype of breast cancers with poor prognosis and targeted drug therapies are limited. To develop novel and efficacious therapies for TNBC, we developed a bispecific antibody F7AK3 that recognizes both trophoblast cell surface antigen 2 (TROP2) and CD3 and evaluated its antitumor activities both in vitro and in vivo.Methods The binding affinities of F7AK3 to the two targets, TROP2 and CD3, were evaluated by surface plasmon resonance. Binding of F7AK3 to TNBC cells and T cells were evaluated by flow cytometry. Immunofluorescent staining was performed to demonstrate the interactions between T cells with TNBC cells. The cytotoxicity of T cells against TNBC cell lines and primary tumor cells mediated by F7AK3 were determined in vitro. In vivo antitumor activity of F7AK3 was investigated in a xenograft TNBC tumor model, using immunodeficient mice that were reconstituted with human peripheral blood mononuclear cells.Results We demonstrated that F7AK3 binds specifically to human TROP2 and CD3 antigens, as well as TNBC cell lines and primary tumor cells. Human T cells can only be activated by F7AK3 in the presence of target tumor cells. F7AK3 recruits T cells to TROP2+ tumor cells in vitro and into tumor tissues in vivo. Antitumor growth activity of F7AK3 is observed in a xenograft TNBC tumor model.Conclusion This study showed the antitumor potential of an anti-TROP2xCD3 bispecific antibody F7AK3 to TNBC tumor cells both in vitro and in vivo. These data demonstrate that F7AK3 has the potential to treat TNBC patients, which warrants further preclinical and clinical evaluation of the F7AK3 in advanced or metastatic TNBC patients.https://jitc.bmj.com/content/9/10/e003468.full |
| spellingShingle | Jing Wang Lin Li Huicheng Liu Lili Bai Liu Huang Na Ning Yijia Li Xuejiao Dong Qiuyang Du Minghui Xia Yufei Chen Likun Zhao Yanhu Li Qingwu Meng Yaqi Duan Jie Ming Andy Qingan Yuan Xiang-Ping Yang Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer Journal for ImmunoTherapy of Cancer |
| title | Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer |
| title_full | Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer |
| title_fullStr | Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer |
| title_full_unstemmed | Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer |
| title_short | Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer |
| title_sort | bispecific antibody targeting trop2xcd3 suppresses tumor growth of triple negative breast cancer |
| url | https://jitc.bmj.com/content/9/10/e003468.full |
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