Methods for treatment of polyposis
The present invention relates to method for treating medical disorders mediated by mutations in the APC gene by administering an IGF1R inhibitor. Such disorders include, for example, familial adenomatous polyposis (FAP).
1. A method for treating familial adenomatous polyposis, in a subject, comprising administering, to a mammalian subject with familial adenomatous polyposis, a therapeutically effective amount of an isolated antibody or antigen-binding fragment thereof that specifically binds human insulin-like growth factor-1 receptor comprising a light chain immunoglobulin that comprises CDR-L1, CDR-L2 and CDR-L3 of the amino acid sequence set forth in SEQ ID NO: 8; and, a heavy chain immunoglobulin that comprises CDR-H1, CDR-H2 and CDR-H3 of the amino acid sequence set forth in SEQ ID NO: 10 and which reduces the number or surface area of adenomas in the small intestine or colon of the subject.
2. The method of claim 1 wherein the antibody or antigen-binding fragment thereof is an antibody comprising a light chain immunoglobulin that comprises the amino acid sequence set forth in SEQ ID NO: 8; and, a heavy chain immunoglobulin that comprises the amino acid sequence set forth in SEQ ID NO: 10.
3. The method of claim 2 wherein the antibody comprises a light chain immunoglobulin variable region linked to a kappa light chain constant region.
4. The method of claim 3 wherein the antibody or fragment comprises a heavy chain immunoglobulin variable region linked to a gamma 1 heavy chain constant region.
5. The method of claim 4 wherein the antibody is administered to the subject in association with one or more therapeutic procedures, diagnostic procedures or additional chemotherapeutic agents.
6. The method of claim 5 wherein an additional chemotherapeutic agent is one or members selected from the group consisting of piroxicam, sulindac, sulindac sulfone, indomethacin, rofecoxib, celecoxib, aspirin, a dietary calcium supplement, a retinoid, a carotenoid, ascorbic acid, α-tocopherol, selenium, folate and methionine.
7. The method of claim 5 wherein the antibody and additional chemotherapeutic agent are in a single pharmaceutical composition along with a pharmaceutically acceptable carrier.
8. The method of claim 5 wherein the antibody and additional chemotherapeutic agent are in two or more separate pharmaceutical compositions each along with pharmaceutically acceptable carriers.
9. The method of claim 4 wherein the antibody is administered to the subject by a parenteral route.
10. The method of claim 1 wherein the antibody or antigen-binding fragment thereof is a member selected from the group consisting of a monoclonal antibody, a polyclonal antibody, an anti-idiotypic antibody, a chimeric antibody, a bispecific antibody, a humanized antibody, a fully human antibody, a recombinant antibody, a Fab, a F(ab) 2 , an Fv, a single chain antibody, a dsFv and a linear antibody.
11. The method of claim 4 wherein the subject is human.