Anthrax Research Today is a free monthly online journal that collates and summarizes the latest research about Anthrax, including details on bacillus anthracis, contagiousness, exposure, effects.

Antitumor activities of TEM8-Fc: an engineered antibody-like molecule targeting tumor endothelial marker 8.

Duan HF, Hu XW, Chen JL, Gao LH, Xi YY, Lu Y, Li JF, Zhao SR, Xu JJ, Chen HP, Chen W, Wu CT

Beijing Institute of Radiation Medicine, Haidian District, Beijing, China. duanhf0720@yahoo.com.cn

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.

Published 17 October 2007 in J Natl Cancer Inst, 99(20): 1551-5.
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