Composition of anti-ENDO180 antibodies and methods of use for the treatment of cancer and fibrotic diseases
The present invention provides antibodies or antigen-binding fragments thereof that specifically bind the ENDO180 polypeptide and are internalized thereby, to conjugates comprising the molecules, to compositions comprising the antibodies and conjugates and to methods of using the same for delivery of therapeutic agents to cells that express the ENDO180 polypeptide on the surface of the cell for treating cell proliferative diseases or disorders and fibrosis, and for controlling (modulating) tumor progression.
1. An anti-ENDO180 antibody or an antigen-binding fragment selected from the group consisting of:
a. an isolated monoclonal antibody produced by the hybridoma cell line E3-8D8, deposited with the BCCM under Accession Number LMBP 7203CB, or an antigen-binding fragment of such isolated monoclonal antibody;
b. a humanized version of the antibody of (a) or an antigen-binding fragment of such humanized version of the antibody of (a); and
c. a chimeric version of the antibody of (a) or an antigen-binding fragment of such chimeric version of the antibody of (a);
wherein upon contact with a cell expressing ENDO180, the antibody or the antigen-binding fragment binds to the ENDO180 on the surface of the cell and is internalized into the cell.
2. A composition comprising the anti-ENDO180 antibody or the antigen-binding fragment of claim 1 , and a pharmaceutically acceptable carrier.
3. The composition of claim 2 , further comprising a moiety selected from the group consisting of a detectable label, a cytotoxic agent, and a therapeutic agent.
4. The composition of claim 3 , wherein the carrier comprises a lipid particle, a polysaccharide particle, or a combination thereof.
5. The composition of claim 4 , wherein the carrier comprises a lipidated polysaccharide particle.
6. The composition of claim 5 , wherein the lipidated polysaccharide particle comprises a lipidated glycosaminoglycan particle.
7. The composition of claim 4 , wherein the anti-ENDO180 antibody or the antigen-binding fragment is immobilized on the particle.
8. The composition of claim 3 or 4 , wherein the moiety is a therapeutic agent.
9. The composition of claim 4 , wherein the moiety is encapsulated within the lipid particle.
10. A hybridoma cell line designated E3-8D8, deposited with the BCCM under Accession Number LMBP 7203CB.
11. The composition of claim 3 , wherein the anti-ENDO180 antibody or the antigen-binding fragment is conjugated to said moiety directly or via a linker which links the anti-ENDO180 antibody or the antigen-binding fragment to said moiety.
12. The composition of claim 11 , wherein the anti-ENDO180 antibody or the antigen-binding fragment is conjugated to said moiety via a linker attached at the carboxyl terminus of the anti-ENDO180 antibody or the antigen-binding fragment.
13. The composition of claim 12 , wherein the linker is selected from the group consisting of a polypeptide linker, a peptide linker, and a lipid linker.
14. A method of treating a subject afflicted with cancer or fibrosis comprising administering to the subject a composition of claim 8 in an amount effective to treat the subject.
15. The anti-ENDO180 antibody or the antigen-binding fragment of claim 1 , wherein the anti-ENDO180 antibody or the antigen-binding fragment is selected from the group consisting of a full IgG, a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, a Fab, a miniantibody, and a scFv.