RT Journal Article
SR Electronic
T1 Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e003468
DO 10.1136/jitc-2021-003468
VO 9
IS 10
A1 Huicheng Liu
A1 Lili Bai
A1 Liu Huang
A1 Na Ning
A1 Lin Li
A1 Yijia Li
A1 Xuejiao Dong
A1 Qiuyang Du
A1 Minghui Xia
A1 Yufei Chen
A1 Likun Zhao
A1 Yanhu Li
A1 Qingwu Meng
A1 Jing Wang
A1 Yaqi Duan
A1 Jie Ming
A1 Andy Qingan Yuan
A1 Xiang-Ping Yang
YR 2021
UL http://jitc.bmj.com/content/9/10/e003468.abstract
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.