SDF-1 binding nucleic acids and the use thereof in cancer treatment
The present invention is related to a nucleic acid molecule capable of binding to SDF-1, preferably capable of inhibiting SDF-1, whereby the nucleic acid molecule is for use in a method for the treatment and/or prevention of a disease or disorder, for use in a method for the treatment of a subject suffering from a disease or disorder or being at risk of developing a disease or disorder as an adjunct therapy, or for use as a medicament for the treatment and/or prevention of a disease or disorder, whereby the disease or disorder is cancer.
1. A method for the treatment of a subject suffering from cancer comprising:
a) administering to the subject a cancer-treating amount of an L-nucleic acid molecule, or a an L-nucleic acid homolog thereof,
wherein said L-nucleic acid molecule comprises SEQ ID NO:22, and said L-nucleic acid homolog comprises SEQ ID NO: 52 and a 5′ terminal stretch of nucleotides and a 3′ terminal stretch of nucleotides, wherein said 5′ stretch and said 3′ stretch can hybridize to each other, wherein
1) when said homolog is shorter than SEQ ID NO: 22, said homolog comprises homology of at least 85% to SEQ ID NO: 22 over the entire length of said homolog, and
2) when said homolog is equal in length to or longer than SEQ ID NO: 22, said homolog comprises homology of at least 85% to SEQ ID NO: 22 over the entire length of SEQ ID NO: 22, and
wherein said L-nucleic acid molecule and said L-nucleic acid homolog bind SDF-1 and inhibit interaction of (a) SDF-1 and CXCR4 and (b) SDF-1 and CXCR7.
2. The method according to claim 1 further comprising:
b) irradiating the subject;
c) surgically treating said subject;
d) treating said subject with a cellular therapy;
e) administering a pharmaceutically active agent to the subject: or
f) combination thereof.
3. The method according to claim 1 , wherein said L-nucleic acid molecule or said L-nucleic acid homolog thereof is administered as an adjunct therapy or part of an adjunct therapy.
4. The method according to claim 3 , wherein the adjunct therapy sensitizes the subject, wherein the sensitized subject is more responsive to a therapy for the treatment of cancer.
5. The method according to claim 1 , wherein the cancer comprises a hematological cancer or a solid tumor.
6. The method according to claim 5 , wherein the hematological cancer comprises leukemia or myeloma.
7. The method according to claim 5 , wherein the solid tumor comprises glioblastoma, colorectal cancer, breast cancer, lymphoma, prostate cancer, pancreatic cancer, renal cancer, ovarian cancer or lung cancer.
8. The method of claim 1 , wherein said L-nucleic acid molecule or said L-nucleic acid homolog comprises a modification.
9. The method of claim 8 , wherein said modification comprises a high molecular weight polyethylene glycol moiety or high molecular weight hydroxyethyl starch moiety.
10. The method of claim 8 , wherein said modification enhances residence time in an animal or human host.
11. The method of claim 2 , wherein said pharmaceutically active agent comprises an antibody, an alkylating agent, an anti-metabolite, a plant alkaloid, a plant terpenoid or a topoisomerase inhibitor.
12. The method of claim 2 , wherein said pharmaceutically active agent comprises leucovorin, methotrexate, tamoxifen, sorafenib, lenalidomide, bortezomib, dexamethasone, fluorouracil or prednisone.
13. A method of treating a patient with cancer, comprising:
(1) administering to said patient an L-nucleic acid molecule or an L-nucleic acid homolog thereof, and
(2) administering a cancer treatment to said patient,
wherein said L-nucleic acid molecule comprises SEQ ID NO: 22, and said L-nucleic acid homolog comprises SEQ ID NO: 52 and a 5′ terminal stretch of nucleotides and a 3′ terminal stretch of nucleotides, wherein said 5′ stretch and said 3′ stretch can hybridize to each other, wherein
i) when said homolog is shorter than SEQ ID NO: 22, said homolog comprises homology of at least 85% to SEQ ID NO: 22 over the entire length of the homolog, and
ii) when said homolog is equal in length to or longer than SEQ ID NO: 22, said homolog comprises homology of at least 85% to SEQ ID NO:22 over the entire length of SEQ ID NO: 22, and
wherein said L-nucleic acid molecule and said L-nucleic acid homolog bind SDF-1 and inhibit interaction of (a) SDF-1 and CXCR4 and (b) SDF-1 and CXCR7.
14. The method according to claim 13 , wherein said cancer comprises a hematological cancer or a solid tumor.
15. The method according to claim 14 , wherein the hematological cancer comprises leukemia or myeloma.
16. The method according to claim 14 , wherein the solid tumor comprises glioblastoma, colorectal cancer, breast cancer, lymphoma, prostate cancer, pancreatic cancer, renal cancer, ovarian cancer or lung cancer.
17. The method of claim 13 , wherein said L-nucleic acid or said L-nucleic acid homolog comprises a modification.
18. The method of claim 17 , wherein said modification comprises a high molecular weight polyethylene glycol moiety or high molecular weight hydroxyethyl starch moiety.
19. The method of claim 13 , wherein said cancer treatment comprises an antibody, an alkylating agent, an anti-metabolite, a plant alkaloid, a plant terpenoid or a topoisomerase inhibitor.
20. The method of claim 13 , wherein said cancer treatment comprises leucovorin, methotrexate, tamoxifen, sorafenib, lenalidomide, bortezomib, dexamethasone, fluorouracil or prednisone.