Methods for inhibiting the binding of endosialin to ligands

Inventors

Zhou, Yuhong • Tomkowicz, Brian • Grasso, Luigi • Nicolaides, Nicholas C. • Sass, Philip M.

Assignees

Eisai Inc

Abstract

The invention provides methods for inhibiting the interaction of endosialin with endosialin ligands. The inhibition is effectuated on the genetic level, by inhibiting endosialin gene expression, and on the protein level, by blocking the interaction of cell-surface expressed endosialin with ligands such as fibronectin and collagen. The invention provides methods for identifying inhibitors of the interaction of endosialin with endosialin ligands. Also provided are methods for inhibiting angiogenesis and neovascularization in vivo and in vitro.

Core Innovation

The invention relates to immunotherapeutic methods to inhibit the interaction of an endosialin-expressing cell with collagen or fibronectin. The methods comprise contacting endosialin-expressing cells with an antibody produced by cells having ATCC Access No. PTA-9017, where binding of the antibody to endosialin expressed on the cell surface inhibits the interaction with collagen or fibronectin.

The invention further provides therapeutic methods for inhibiting neovascularization and angiogenesis by administering a therapeutically effective amount of the ATCC PTA-9017 antibody to a subject. In these methods, inhibiting the endosialin-collagen or endosialin-fibronectin interaction on the surface of cells inhibits neovascularization of a tissue, organ, or neoplasm, and inhibits angiogenesis of a tissue, organ, or neoplasm.

The described downstream biological effects include inhibited cell motility and cell migration, reduced integrin activation, and reduced activation or expression of matrix metalloproteases, including MMP-9. The invention also includes assays for identifying agonists or antagonists of endosialin-ligand interactions using endosialin-test compound complexes and endosialin bound to a cell membrane, a fragment, an artificial lipid bilayer, or a solid support.

Claims Coverage

The provided independent claims center on inhibiting the endosialin-collagen or endosialin-fibronectin interaction using an antibody produced by cells having ATCC Access No. PTA-9017, with inventive features specifying therapeutic inhibition of neovascularization and angiogenesis and the downstream functional consequences including cell migration, integrin activation, and matrix metalloprotease activity including MMP-9.

Across the independent claims, the core inventive approach is to inhibit endosialin interaction with collagen or fibronectin using an ATCC PTA-9017-produced antibody, including by obstructing endosialin on the cell surface. The claim set further ties this inhibition to inhibition of neovascularization and angiogenesis, and to downstream functional consequences including inhibited cell migration and inhibition or reduction of integrin activation and matrix metalloprotease activity, including MMP-9.

Stated Advantages

Documented Applications