Antitumor Activities of TEM8-Fc: An Engineered Antibody-like Molecule Targeting Tumor Endothelial Marker 8.
Duan, Hai-Feng 1; Hu, Xian-Wen 2; Chen, Jin-Long 1; Gao, Li-Hua 2; Xi, Yong-Yi 2; Lu, Ying 3; Li, Jin-Feng 1; Zhao, Su-Rong 1; Xu, Jun-Jie 4; Chen, Hui-Peng 2; Chen, Wei 4; Wu, Chu-Tse 1
[Miscellaneous Article] Journal of the National Cancer Institute. 99(20):1551-1555, October 2007.

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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 [CI]=0.96 to 2.16 g; P<.001; MCF-7, 1.12 versus 0.08 g, difference=1.04 g, 95% CI=0.77 to 1.31 g; P<.001; HepG2, 1.28 versus 0.35 g, difference=0.93 g, 95% CI=0.60 to 1.25 g; P<.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.

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