Integrin-targeting protein and methods of use thereof
AssigneesGeorgia State University Research Foundation, Inc., Proda Biotech LLC
InventorsZhi-Ren Liu, Chakra Ravi Turaga, Jenny Yang
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Abstract
A non-toxic anti-angiogenesis protein that inhibits tumor growth and exhibits in vitro activity in induction of angiogenic endothelial cell apoptosis without targeting VEGF/VEGFR or any other RTK pathways is described. The protein targets integrins αvβ3, at a groove in the βA domain of β3 formed by α2 helix, B—C loop, and α2-α3 loop.
Claims12
A method of decreasing excessive accumulation of fibrous material within the extracellular matrix in injured or damaged tissue of a subject comprising
- a. identifying the subject in need thereof, and
- b. administering to the subject a polypeptide that binds specifically to integrins αvβ3, comprising:
- a variant of domain 1 of cell adhesion protein (D1-CD2) having the amino acid of SEQ ID NO:
- 4,
- wherein the polypeptide specifically binds to integrin αvβ3 at βA domain in the region of α2 helix, B—C loop and α2-α3 loop;
- and
- wherein the method decreases excessive accumulation of fibrous material in subjects having liver fibrosis, pancreatic fibrosis, or breast cancer associated fibrosis, and
- wherein the excess accumulation of fibrous material is not due to the subject having retrolental fibroplasia, idiopathic pulmonary fibrosis, neurofibroma or angiofibroma.
A method of inducing apoptosis in tissue of a subject, comprising administering a therapeutically effective amount of the pharmaceutical composition of a polypeptide that binds specifically to integrins αvβ3, comprising:
- a variant of domain 1 of cell adhesion protein (D1-CD2) having the amino acid of SEQ ID NO:
- 4, wherein the polypeptide specifically binds to integrin αvβ3 at βA domain in the region of α2 helix, B—C loop and α2-α3 loop, and the polypeptide has a dissociation constant is less than 1 μM, and excess accumulation of fibrous material is not retrolental fibroplasia, idiopathic pulmonary fibrosis, neurofibroma or angiofibroma and the subject has liver fibrosis, pancreatic fibrosis or breast cancer associated fibrosis.
Dependencies are inferred from the claim text.