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.