From AACR Use of ENMD human AS in mice
315 Recombinant human AngiostatinTM protein expressed in Pichia pastoris inhibits B16BL6
melanoma in an experimental metastasis model. Fogler, W.E., Liang, H., Zhou, X.H., Lu, M., Madsen, J.W.,
Chang, A., Dey, C., Plum, S., Amelink, H., Nelson, B., Fortier, A.H., and Sim, B.K.L. EntreMed, Inc., 9610 Medical
Center Dr. Rockville, MD 20850.
Angiostatin has been shown to inhibit primary tumor growth in a number of murine models. This potent anti-angiogenic has
also been shown to inhibit metastatic disease following removal of the primary Lewis Lung (LLC-LM) tumors in mice. We
tested two different Pichia pastoris clones expressing human AngiostatinTM protein in an experimental metastasis model
using the B16BL6 melanoma. Mice were inoculated intravenously with B16BL6 melanoma. AngiostatinTM protein therapy
was initiated 3 days after tumor inoculation at 1.5 mg/kg every 12 hr for 11 consecutive days. On day 14 all mice were
sacrificed, lungs were removed, fixed in formalin, and surface metastases were counted with a dissecting microscope. In five
separate experiments, lung metastases were inhibited by 60-80% in mice treated with AngiostatinTM protein from either
clone. Dose escalation studies are underway. These data are the first to show efficacy of recombinant AngiostatinTM protein
in an experimental model of metastasis. |
