PT  - JOURNAL ARTICLE
AU  - Huicheng Liu
AU  - Lili Bai
AU  - Liu Huang
AU  - Na Ning
AU  - Lin Li
AU  - Yijia Li
AU  - Xuejiao Dong
AU  - Qiuyang Du
AU  - Minghui Xia
AU  - Yufei Chen
AU  - Likun Zhao
AU  - Yanhu Li
AU  - Qingwu Meng
AU  - Jing Wang
AU  - Yaqi Duan
AU  - Jie Ming
AU  - Andy Qingan Yuan
AU  - Xiang-Ping Yang
TI  - Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer
AID  - 10.1136/jitc-2021-003468
DP  - 2021 Oct 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - e003468
VI  - 9
IP  - 10
4099  - http://jitc.bmj.com/content/9/10/e003468.short
4100  - http://jitc.bmj.com/content/9/10/e003468.full
SO  - J Immunother Cancer2021 Oct 01; 9
AB  - 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.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information.