Compositions and methods for treating cancer and other diseases
Aptamers and improved aptamers are provided with enhanced efficacy for binding to target molecules in vivo or for treating cancer or other diseases. Such improvements in aptamers are provided that enhance in vivo efficacy such as binding to the target molecule or enhancing anti-cancer activity. Such improvements also include stability to serum nucleases, reduced binding to a soluble form of the target molecule, increased avidity, affinity or specificity to the target molecule on a cell surface, increased lifetime in circulation, or any combination of the foregoing. Improvements are provided by truncation, multimerization, including at least one non-natural nucleic acid, adding a 3′ or 5′ polyethylene glycol, or any combination thereof. Aptamers for treatment of autoimmune diseases are also provided.
1. A bivalent aptamer having the sequence represented by SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15 or SEQ ID NO:18.
2. A monovalent aptamer having the sequence represented by SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9 or SEQ ID NO:17.
3. A pharmaceutical composition comprising the monovalent aptamer of claim 2 and a pharmaceutically acceptable carrier, diluent or excipient.
4. An aptamer of claim 1 , further comprising a therapeutic or diagnostic moiety.
5. An aptamer of claim 2 further comprising a therapeutic or diagnostic moiety.
6. The aptamer of claim 4 wherein the further moiety is a cytotoxic agent, a radionuclide, a fluorophore, an antibody, or a siRNA.
7. The aptamer of claim 5 wherein the further moiety is a cytotoxic agent, a radionuclide, a fluorophore, an antibody, or a siRNA.
8. A pharmaceutical composition comprising an aptamer of claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.
9. A method for treating or diagnosing a B cell disease comprising administering to a subject in need thereof the pharmaceutical composition of claim 8 .
10. The method of claim 9 wherein the B cell disease is cancer.
11. The method of claim 9 wherein the B cell disease is an autoimmune disease, an immune deficiency disease, a disease benefited by immunosuppression or as an adjunct to vaccination or tolerization.
12. A method for treating or diagnosing a B cell disease comprising administering to a subject in need thereof the pharmaceutical composition of claim 3 .
13. The method of claim 12 wherein the B cell disease is cancer.
14. The method of claim 12 wherein the B cell disease is an autoimmune disease, an immune deficiency disease, a disease benefited by immunosuppression or as an adjunct to vaccination or tolerization.
15. A method for treating a cancer comprising administering to a subject in need thereof the pharmaceutical composition of claim 8 .
16. The method of claim 15 wherein the cancer is Burkitt lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma.
17. A method for treating an autoimmune disease comprising administering to a subject in need thereof a pharmaceutical composition of claim 8 .
18. A method for treating a cancer comprising administering to a subject in need thereof the pharmaceutical composition of claim 3 .
19. A method for treating an autoimmune disease comprising administering to a subject in need thereof a pharmaceutical composition of claim 3 .