TARGETING AN AMPHIREGULIN-DERIVED CELL SURFACE NEO-EPITOPE
Antibodies to an amphiregulin neo-epitope, fragments thereof, and compositions comprising such are provided. Therapies for cancers in which cells thereof express amphiregulin are provided, as well as assays for identifying additional agents useful in such therapies.
1 . An isolated antibody, or an isolated fragment of an antibody, or an aptamer, which binds to a membrane-associated extracellular portion of a cleaved amphiregulin precursor protein.
2 . The isolated antibody, or isolated fragment of an antibody, or aptamer of claim 1 , wherein the non-cleaved amphiregulin precursor protein comprises SEQ ID NO:1.
3 . The isolated antibody, or isolated fragment of an antibody, or aptamer of claim 1 , wherein the membrane-associated extracellular portion of the cleaved amphiregulin precursor protein does not comprise residues 1-187 of SEQ ID NO:1.
4 . The isolated antibody, or isolated fragment of an antibody, or aptamer of claim 1 , wherein the antibody binds an epitope comprising two or more residues of residues 188 to 199 as set forth in SEQ ID NO:1.
5 . The isolated antibody, or isolated fragment of an antibody, or aptamer, of claim 1 , wherein the antibody binds a conformational epitope formed by two or more residues of residues 188 to 199 as set forth in SEQ ID NO:1.
6 . The isolated antibody, or isolated fragment of an antibody, or aptamer, of claim 1 , wherein the antibody or aptamer binds SEQ ID NO:2 but does not bind SEQ ID NO:1.
7 . An isolated antibody of claim 1 , wherein the antibody is a human antibody, a humanized antibody or a chimeric antibody.
8 . The isolated antibody of claim 7 , wherein the antibody is a monoclonal antibody.
9 . The isolated antibody of claim 7 , wherein the antibody is a human antibody.
10 . An isolated fragment of an antibody of claim 1 , wherein the fragment is a fragment of a human antibody, of a humanized antibody or of a chimeric antibody.
11 . The isolated fragment of an antibody of claim 10 , wherein the fragment is of a monoclonal antibody.
12 . The isolated fragment of an antibody of claim 10 , wherein the fragment is of a human antibody.
13 . The isolated fragment of an antibody of claim 10 , wherein the fragment comprises an Fab, an Fab′, an F(ab′) 2 , an F d , an F v , a complementarity determining region (CDR), or a single-chain antibody (scFv).
14 . The isolated antibody, or isolated fragment of an antibody, of claim 10 conjugated to a detectable agent or conjugated to a cytotoxic agent.
15 . A composition comprising the isolated antibody of claim 1 , or an isolated fragment thereof of claim 1 .
16 . A pharmaceutical composition comprising the isolated antibody of claim 1 , or an isolated fragment thereof.
17 . A method of treating a solid tumor in a subject comprising administering to the subject the antibody, or an antigen-binding fragment thereof, or aptamer of claim 1 effective to treat the solid tumor.
18 . The method of claim 17 , wherein the tumor is an ER+ tumor.
19 . (canceled)
20 . The method of claim 17 , wherein the tumor is a tumor of the lung or is a colorectal tumor.
21 - 38 . (canceled)
39 . A method is provided of treating a tumor in a subject comprising administering to the subject an amount of dendritic cells loaded with cleaved amphiregulin precursor protein effective to treat a tumor.