Therapies for B cell malignancies
View Patent ↗The subject invention provides novel methods for treating B cell malignancies, such as multiple myeloma, using a combination therapy. Said treatment in accordance with the subject invention comprises the administration of a B cell regulator, e.g., a galectin molecule, to a subject suffering from a B cell malignancy, and wherein said subject received, receives, or will receive a treatment with a conventional treatment for such B cell malignancy, e.g., immunotherapy. The administration of the galectin molecule boosts the expression of B cell specific antigens e.g., SLAMF7, on MM cells, thereby increasing the sensitivity of MM cells to anti-SLAMF7 Ab and therapeutic efficacy of Elotuzumab.
1. A method for treating a B cell malignancy in a subject in need of such treatment, comprising A) administering to the subject a composition comprising a functional galectin molecule to increase the expression of signaling lymphocytic activation molecule F7 (SLAMF7) in B cells and/or multiple myeloma cells; and B) administering to the subject a composition comprising an anti-SLAMF7 antibody, the functional galectin molecule being galectin-9 protein or a nucleotide sequence encoding the galectin-9 protein.
2. The method of claim 1 , the B cell malignancy being a B cell derived cancer.
3. The method of claim 1 , the B cell malignancy being multiple myeloma.
4. The method of claim 1 , the anti-SLAMF7 antibody being Elotuzumab.
5. The method of claim 1 , each administration being independently selected from local, oral, nasal, topical, intratumoural, transdermal, intra-articular, intravenous, intraperitoneal, intradermal, subcutaneous, and intramuscular routes.
6. A method for treating multiple myeloma in a subject, comprising
A) administering to the subject a composition comprising 1) a nucleic acid sequence that encodes Gal-9 or a nucleic acid sequence that encodes a protein sharing at least 95% identity with Gal-9, 2) an amino acid sequence of Gal-9 or an amino acid sequence sharing at least 95% identity with Gal-9, 3) a vector comprising a nucleic acid sequence that encodes Gal-9 or a nucleic acid sequence that encodes a protein sharing at least 95% identity with Gal-9, 4) a cell that overexpresses a nucleic acid sequence of Gal-9 or a nucleic acid sequence that encodes a protein sharing at least 95% identity with Gal-9, and/or 5) a cell that overexpresses an amino acid sequence of Gal-9, to increase the expression of SLAMF7 in multiple myeloma cells; and
B) administering to the subject an anti-SLAMF7 antibody.
7. The method of claim 6 , the anti-SLAMF7 antibody being Elotuzumab.
8. The method of claim 6 , each administration being independently selected from local, oral, nasal, topical, intratumoural, transdermal, intra-articular, intravenous, intraperitoneal, intradermal, subcutaneous, and intramuscular routes.
9. A method for improving the sensitivity of multiple myeloma cells of a subject to an immunotherapy, the method comprising:
A) administering to the subject a composition comprising 1) a nucleic acid sequence that encodes Gal-9 or a nucleic acid sequence that encodes a protein sharing at least 95% identity with Gal-9, 2) an amino acid sequence of Gal-9 or an amino acid sequence sharing at least 95% identity with Gal-9, 3) a vector comprising a nucleic acid sequence that encodes Gal-9 or a nucleic acid sequence that encodes a protein sharing at least 95% identity with Gal-9, 4) a cell that overexpresses a nucleic acid sequence of Gal-9 or a nucleic acid sequence that encodes a protein sharing at least 95% identity with Gal-9, and/or 5) a cell that overexpresses an amino acid sequence of Gal-9, to increase the expression of SLAMF7 in multiple myeloma cells; and
B) administering to the subject the immunotherapy.
10. The method of claim 9 , the immunotherapy being an antibody therapy.
11. The method of claim 10 , the antibody therapy comprising administering to the subject an anti-SLAMF7 antibody.
12. The method of claim 11 , the anti-SLAMF7 antibody being Elotuzumab.
13. The method of claim 9 , further comprising detecting SLAMF7 level before and/or after step A).
14. The method of claim 1 , further comprising detecting the expression of SLAMF7 before and/or after administering the composition comprising the functional galectin molecule.
15. The method of claim 6 , further comprising detecting the expression of SLAMF7 before and/or after step A).
16. The method of claim 1 , further comprising detecting SLAMF7 level before and/or after step A).
17. The method of claim 1 , wherein administering the composition increases the expression of SLAMF7 in B cells and multiple myeloma cells.
18. The method of claim 1 , wherein administering the composition increases the expression of SLAMF7 in multiple myeloma cells.
19. The method of claim 1 , wherein administering the composition increases the expression of SLAMF7 in B cells.