Combinations of PBD-based antibody drug conjugates with Bcl-2 inhibitors
This invention relates to treatment of cancer using antibody drug conjugates that comprise PBD molecules in combination with Bcl-2 inhibitors.
1. A method of treating cancer in a subject in need of such treatment, the method comprising administering an antibody drug conjugate (ADC) and a Bcl-2 inhibitor, wherein the ADC comprises an antibody conjugated to a PBD cytotoxic agent, wherein the Bcl-2 inhibitor is selected from the group consisting of ABT-199 and ABT-263, and wherein the antibody is selected from the group consisting of:
a) an anti-CD33 antibody comprising the light chain variable region of SEQ ID NO: 1 and the heavy chain variable region of SEQ ID NO: 2; and
b) and anti-CD19 antibody comprising the light chain variable region of SEQ ID NO: 10 and the heavy chain variable region of SEQ ID NO: 11.
2. The method of claim 1 , wherein the PBD cytotoxic agent has the formula
3. The method of claim 1 , wherein the Bcl-2 inhibitor is ABT-199.
4. The method of claim 1 , wherein the Bcl-2 inhibitor is ABT-263.
5. The method of claim 2 , wherein the antibody is an anti-CD33 antibody comprising the light chain variable region of SEQ ID NO: 1 and the heavy chain variable region of SEQ ID NO: 2.
6. The method of claim 5 , wherein the antibody is h2H12.
7. The method of claim 6 , wherein the Bcl-2 inhibitor is ABT-199.
8. The method of claim 1 , wherein the antibody is an anti-CD33 antibody comprising the light chain variable region of SEQ ID NO: 1 and the heavy chain variable region of SEQ ID NO: 2.
9. The method of claim 8 , wherein the cancer is acute myeloid leukemia or myelodysplastic syndrome.
10. The method of claim 1 , wherein the antibody is an anti-CD19 antibody comprising the light chain variable region of SEQ ID NO: 10 and the heavy chain variable region of SEQ ID NO: 11.
11. The method of claim 10 , wherein the cancer is selected from the group consisting of non-hodgkins lymphoma, diffuse large B-cell lymphoma, acute lymphocytic leukemia, and chronic lymphocytic lymphoma.