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, comprising administering to a subject having the CD38-expressing B-cell lymphoma, multiple myeloma, early stage multiple myeloma, pre-multiple myeloma, Waldenstrom's macroglobulinemia, non-Hodgkin's lymphoma, chronic myelogenous leukemia, chronic lymphocytic leukemia or acute lymphocytic leukemia lenalidomide or pomalidomide and a construct comprising an antibody that specifically binds to CD38 comprising the heavy chain CDR1, CDR2, and CDR3 of SEQ ID NO: 18 and the light chain CDR1, CDR2, and CDR3 of SEQ ID NO: 22 and an attenuated interferon alpha 2b in an amount effective to treat the 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.
2. The method of claim 1 , wherein the antibody comprises 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: 22.
3. The method of claim 2 , wherein the antibody comprises 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: 29.
4. The method of claim 3 , wherein the antibody comprises a human IgG4 constant region.
5. The method of claim 4 , wherein the human IgG4 constant region comprises a proline at position 228 according to the EU numbering system.
6. The method of claim 5 , 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.
7. The method of claim 3 , wherein the antibody comprises a human IgG1 constant region.
8. The method of claim 7 , 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.
9. The method of 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.
10. The method of claim 3 , wherein the attenuated interferon alpha-2b comprises the amino acid sequence of SEQ ID NO: 212 or SEQ ID NO: 213.
11. The method of claim 3 , wherein the attenuated interferon alpha-2b comprises the amino acid sequence of SEQ ID NO: 212.
12. The method of claim 1 , wherein the subject has CD38-expressing multiple myeloma.
13. The method of claim 3 , wherein the subject has CD38-expressing multiple myeloma.
14. The method of claim 11 , wherein the subject has CD38-expressing multiple myeloma.
15. The method of claim 1 , wherein the CD38-expressing B-cell lymphoma, multiple myeloma, early stage multiple myeloma, pre-multiple myeloma, Waldenstrom's macroglobulinemia, non-Hodgkin's lymphoma, chronic myelogenous leukemia, chronic lymphocytic leukemia or acute lymphocytic leukemia is resistant to lenalidomide.
16. The method of claim 1 , wherein the subject is a human being.
17. The method of claim 1 , wherein the method comprises administering to a human subject having CD38-expressing multiple myeloma lenalidomide and the construct in an amount effective to treat the multiple myeloma, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 27, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 29, and a human IgG4 constant region, and the attenuated interferon alpha-2b comprises the amino acid sequence of SEQ ID NO: 212.
18. The method of claim 1 , wherein the method comprises administering to a human subject having CD38-expressing multiple myeloma pomalidomide and the construct in an amount effective to treat the multiple myeloma, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 27, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 29, and a human IgG4 constant region, and the attenuated interferon alpha-2b comprises the amino acid sequence of SEQ ID NO: 212.
19. The method of claim 1 , wherein the construct comprises the amino acid sequence of SEQ ID NO: 216, and the antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 29.
20. The method of claim 19 , wherein the subject has CD38-expressing multiple myeloma.