Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer

Huicheng Liu; Lili Bai; Liu HuangNa NingLin LiYijia LiXuejiao DongQiuyang DuMinghui XiaYufei ChenLikun ZhaoYanhu LiQingwu MengJing WangYaqi DuanJie MingAndy Qingan YuanXiang-Ping Yang

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Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer

机译：Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer

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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 sup+/sup 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.

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来源
《journal for immunotherapy of cancer》 |2021年第10期|1-12|共12页
作者
Huicheng Liu; Lili Bai; Liu HuangNa NingLin LiYijia LiXuejiao DongQiuyang DuMinghui XiaYufei ChenLikun ZhaoYanhu LiQingwu MengJing WangYaqi DuanJie MingAndy Qingan YuanXiang-Ping Yang;
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作者单位

Department of Immunology, School of Basic Medicine, Huazhong University of Science and Technology Tongji Medical College;

Excyte Biopharma Ltd;

Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology Tongji Medical CollegeDepartment of Pathology, School of Basic Medicine, Huazhong University of Science and Technology Tongji Medical CollegeInstitute of Pathology, Tongji Hospital, Huazhong University of Science and Technology Tongji Medical CollegeDepartment of Breast and Thyroid Surgery, Wuhan Union Hospital, Huazhong University of Science and Technology Tongji Medical College;

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正文语种英语
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antibodies; breast neoplasms; immunotherapy; lymphocytes; neoplasm; tumor microenvironment; tumor-infiltrating;

Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer

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