Characterization of a novel bispecific antibody targeting tissue factor-positive tumors with T cell engagement

被引:15
作者
Pan, Zhidi [1 ]
Chen, Jie [1 ]
Xiao, Xiaodong [2 ,3 ]
Xie, Yueqing [2 ]
Jiang, Hua [2 ,3 ]
Zhang, Baohong [1 ]
Lu, Huili [1 ]
Yuan, Yunsheng [1 ]
Han, Lei [3 ]
Zhou, Yuexian
Zong, Huifang [1 ]
Wang, Lei [1 ]
Sun, Rui [1 ]
Zhu, Jianwei [1 ,2 ,3 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Pharm, Engn Res Ctr Cell & Therapeut Antibody, MOE, Shanghai 200240, Peoples R China
[2] Jecho Labs Inc, Frederick, MD 21704 USA
[3] Jecho Biopharmaceut Co Ltd, Tianjin 300467, Peoples R China
基金
中国国家自然科学基金;
关键词
T cell engaging bispecific antibody; Immunotherapy; Tissue factor; Solid tumor; Pancreatic cancer; Lung cancer; PD-1; antibody; PREVIOUSLY TREATED RECURRENT; FACTOR EXPRESSION; TISOTUMAB VEDOTIN; CANCER; CARCINOMA; COMBINATION; METASTASIS; PROGNOSIS; NIVOLUMAB; SAFETY;
D O I
10.1016/j.apsb.2021.10.028
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
T cell engaging bispecific antibody (TCB) is an effective immunotherapy for cancer treatment. Through co-targeting CD3 and tumor-associated antigen (TAA), TCB can redirect CD3(+) T cells to eliminate tumor cells regardless of the specificity of T cell receptor. Tissue factor (TF) is a TAA that involved in tumor progression. Here, we designed and characterized a novel TCB targeting TF (TF-TCB) for the treatment of TF-positive tumors. In vitro, robust T cell activation, tumor cell lysis and T cell proliferation were induced by TF-TCB. The tumor cell lysis activity was dependent upon both CD3 and TF binding moieties of the TF-TCB, and was related to TF expression level of tumor cells. In vivo, in both tumor cell/human peripheral blood mononuclear cells (PBMC) co-grafting model and established tumor models with poor T cell infiltration, tumor growth was strongly inhibited by TF-TCB. T cell infiltration into tumors was induced during the treatment. Furthermore, efficacy of TF-TCB was further improved by combination with immune checkpoint inhibitors. For the first time, our results validated the feasibility of using TF as a target for TCB and highlighted the potential for TF-TCB to demonstrate efficacy in solid tumor treatment. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
引用
收藏
页码:1928 / 1942
页数:15
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