Antitumor activities of TEMS-Fc: An engineered antibody-like molecule targeting tumor endothelial marker 8

作者：Duan, Hai-Feng^*; Hu, Xian-Wen; Chen, Jin-Long; Gao, Li-Hua; Xi, Yong-Yi; Lu, Ying; Li, Jin-Feng; Zhao, Su-Rong; Xu, Jun-Jie; Chen, Hui-Peng; Chen, Wei; Wu, Chu-Tse

来源：JNCI-Journal of the National Cancer Institute, 2007, 99(20): 1551-1555.

DOI：10.1093/jnci/djm132

• ENDOTHELIAL GROWTH-FACTOR
• PYRUVATE-KINASE
• TUMOR ANGIOGENESIS
• ANTHRAX TOXIN
• RECEPTOR
• THERAPY
• DRUG
• EXPRESSION
• RESISTANCE
• STRATEGY

Tumor endothelial marker 8 (TEM8) was discovered as a cell membrane protein that is predominantly expressed in tumor endothelium and identified as a receptor for anthrax toxin. We developed an antibody-like molecule that consists of the protective antigen (PA)-binding domain of human TEM8 linked to the Fc portion of human immunoglobulin G1 (TEM8-Fc). This engineered protein bound to PA in a divalent cation-dependent manner and efficiently protected J774A.1 macrophage-like cells against anthrax toxin challenge in a dose-dependent manner. TEM8-Fc suppressed the growth and metastasis of xenograft human tumors in athymic nude mice (control versus 10 mg/kg TEM8-Fc, mean tumor weight: LS-180, 1.72 versus 0.16 g, difference = 1.56 g, 95% confidence interval [Cl] = 0.96 to 2.16 g; P<001; MCF-7, 1.12 versus 0.08 g, difference = 1.04 g, 95% Cl = 0.77 to 1.31 g; P<001; HepG2, 1.28 versus 0.35 g, difference = 0.93 g, 95% Cl = 0.60 to 1.25 g; N.001). Furthermore, TEM8 interacted with the M2 isoenzyme of pyruvate kinase (M2-PK), which has an important role in tumor growth and metastasis. TEM8-Fc is a novel therapeutic antibody-like agent in the management of solid tumors that may act by trapping M2-PK.

• 出版日期2007-10-17
• 单位中国人民解放军军事医学科学院; 北京中医药大学