Combination of lenalidomide and polypeptide construct, and uses thereof
Methods for cancer treatment include administering to a cancer patient an anti-CD38 antibody-attenuated human IFN alpha-2b construct and lenalidomide or pomalidomide. Tumors that may be treated according to these methods include tumors which comprise CD-38 expressing tumor cells, including B-cell lymphoma, multiple myeloma, non-Hodgkin's lymphoma, chronic myelogenous leukemia, chronic lymphocytic leukemia, and acute lymphocytic leukemia.
1. A method for treating a CD38-expressing B-cell lymphoma, multiple myeloma, early stage multiple myeloma, pre-multiple myeloma, Waldenström's macroglobulinemia, non-Hodgkin's lymphoma, chronic myelogenous leukemia, chronic lymphocytic leukemia, or acute lymphocytic leukemia in a subject, the method comprising administering to the subject lenalidomide or pomalidomide and an antibody that specifically binds to CD38, the antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 18 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 29, and the antibody being fused to an attenuated interferon alpha 2b.
2. The method according to claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 27.
3. The method according to claim 1 , wherein the antibody comprises a light chain comprising a constant region.
4. The method according to claim 3 , wherein the light chain comprises the amino acid sequence of SEQ ID NO: 217.
5. The method according to claim 1 , wherein the antibody comprises a human IgG4 constant region.
6. The method according to claim 5 , wherein the human IgG4 constant region comprises a proline at position 228 according to the EU numbering system.
7. The method according to claim 6 , wherein the human IgG4 constant region further comprises a tyrosine at position 252, a threonine at position 254, and a glutamic acid at position 256 of the constant region according to the EU numbering system.
8. The method according to claim 1 , wherein the antibody comprises a human IgG1 constant region.
9. The method according to claim 8 , wherein the human IgG1 constant region comprises a tyrosine at position 252, a threonine at position 254, and a glutamic acid at position 256 of the constant region according to the EU numbering system.
10. The method according to claim 1 , wherein the attenuated interferon alpha-2b comprises the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 212, or SEQ ID NO: 213.
11. The method according to claim 1 , wherein the attenuated interferon alpha-2b comprises the amino acid sequence of SEQ ID NO: 212 or SEQ ID NO: 213.
12. The method according to claim 1 , wherein the attenuated interferon alpha-2b comprises the amino acid sequence of SEQ ID NO: 212.
13. The method according to claim 1 , wherein the subject has CD38-expressing multiple myeloma.
14. A method for treating a CD38-expressing B-cell lymphoma, multiple myeloma, early stage multiple myeloma, pre-multiple myeloma, Waldenström's macroglobulinemia, non-Hodgkin's lymphoma, chronic myelogenous leukemia, chronic lymphocytic leukemia, or acute lymphocytic leukemia in a subject, the method comprising administering to the subject lenalidomide or pomalidomide and an antibody that specifically binds to CD38, the antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 27 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 22, and the antibody being fused to an attenuated interferon alpha 2b.
15. The method according to claim 14 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 29.
16. The method according to claim 14 , wherein the antibody comprises a light chain comprising a constant region.
17. The method according to claim 16 , wherein the light chain comprises the amino acid sequence of SEQ ID NO: 217.
18. The method according to claim 14 , wherein the attenuated interferon alpha-2b comprises the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 212, or SEQ ID NO: 213.
19. The method according to claim 14 , wherein the attenuated interferon alpha-2b comprises the amino acid sequence of SEQ ID NO: 212 or SEQ ID NO: 213.
20. The method according to claim 14 , wherein the attenuated interferon alpha-2b comprises the amino acid sequence of SEQ ID NO: 212.
21. The method according to claim 14 , wherein the subject has CD38-expressing multiple myeloma.