Compositions comprising anti-CEACAM1 and anti-PD antibodies for cancer therapy
The present invention provides compositions comprising anti-CEACAM1 antibodies, compositions comprising antibodies capable of inhibiting or blocking the interaction between PD-1 and its ligands, and methods for their combined use in treating cancer.
1. A composition comprising:
a pharmaceutical composition comprising a monoclonal antibody to human CEACAM1 or an antigen-binding fragment thereof having a heavy-chain CDR1 comprising a sequence set forth in SEQ ID NO: 1, a heavy-chain CDR2 comprising a sequence set forth in SEQ ID NO: 2, a heavy-chain CDR3 comprising a sequence set forth in SEQ ID NO: 3, a light-chain CDR1 comprising a sequence set forth in SEQ ID NO: 4, a light-chain CDR2 comprising a sequence set forth in SEQ ID NO: 5 and a light-chain CDR3 comprising a sequence set forth in SEQ ID NO: 6; and
a pharmaceutical composition comprising a monoclonal antibody to at least one of human PD-1, PD-L1 and PD-L2 or an antigen-binding fragment thereof, capable of disrupting the binding of PD-1 to its ligands;
wherein said pharmaceutical compositions are in separate containers.
2. The composition of claim 1 , comprising a monoclonal antibody to human CEACAM1 and a monoclonal antibody to human PD-1.
3. The composition of claim 1 , wherein said monoclonal antibody to human CEACAM1 or an antigen-binding fragment thereof is capable of binding with an affinity of at least about 10 −8 M to human CEACAM1.
4. The composition of claim 1 , wherein said monoclonal antibody to human CEACAM1 or an antigen-binding fragment thereof is capable of binding with an affinity of at least about 5×10 −7 M to at least one of human CEACAM3 and human CEACAM5.
5. The composition of claim 1 , wherein said monoclonal antibody to human CEACAM1 is CM-24 or an antigen-binding fragment thereof.
6. The composition of claim 2 , wherein said monoclonal antibody to human PD-1 is selected from the group consisting of MK-3475, AMP514, BMS-936558, CT-011, antigen-binding fragments thereof, and any combination thereof.
7. The composition of claim 1 , wherein said monoclonal antibodies are human or humanized monoclonal antibodies.
8. The composition of claim 1 , further comprising a human lymphocyte cell.
9. A method for treating a patient having cancer, comprising the steps of separately administering to said patient:
(i) a pharmaceutical composition comprising a monoclonal antibody to human CEACAM1 or an antigen-binding fragment thereof, capable of blocking CEACAM1 ligand having a heavy-chain CDR1 comprising a sequence set forth in SEQ ID NO: 1, a heavy-chain CDR2 comprising a sequence set forth in SEQ ID NO: 2, a heavy-chain CDR3 comprising a sequence set forth in SEQ ID NO: 3, a light-chain CDR1 comprising a sequence set forth in SEQ ID NO: 4, a light-chain CDR2 comprising a sequence set forth in SEQ ID NO: 5 and a light-chain CDR3 comprising a sequence set forth in SEQ ID NO: 6; and
(ii) a pharmaceutical composition comprising a monoclonal antibody to at least one of human PD-1, PD-L1 and PD-L2 or an antigen-binding fragment thereof, capable of disrupting the binding of PD-1 to its ligands; thereby treating said cancer.
10. The method of claim 9 , comprising separately administering to said patient:
(i) a pharmaceutical composition comprising said monoclonal antibody to human CEACAM1 or an antigen-binding fragment thereof; and
(ii) a pharmaceutical composition comprising said monoclonal antibody to human PD-1 or an antigen-binding fragment thereof.
11. The method of claim 9 , wherein said monoclonal antibody to human PD-1, PD-L1 and PD-L2 is administered to said patient before said monoclonal antibody to human CEACAM1.
12. The method of claim 9 , wherein said monoclonal antibody to human PD-1, PD-L1 and PD-L2 is administered to said patient simultaneously with said monoclonal antibody to human CEACAM1.
13. The method of claim 9 , wherein said monoclonal antibody to human PD-1, PD-L1 and PD-L2 is administered to said patient after said monoclonal antibody to human CEACAM1.
14. The method of claim 9 , further comprising administering to said patient a pharmaceutical composition comprising a lymphocyte cell.
15. The method of claim 9 , wherein said cancer expresses CEACAM1, PD-1, PD-L1, PD-L2, or any combination thereof.
16. The method of claim 9 , wherein said cancer is selected from the group consisting of a melanoma, lymphoma, lung, thyroid, breast, colon, prostate, hepatic, bladder, renal, cervical, pancreatic, leukemia, myeloid, ovarian, uterus, sarcoma, biliary, and endometrial cells cancers.
17. A kit comprising:
(i) a pharmaceutical composition comprising a monoclonal antibody to human CEACAM1 or an antigen-binding fragment thereof, having a heavy-chain CDR1 comprising a sequence set forth in SEQ ID NO: 1, a heavy-chain CDR2 comprising a sequence set forth in SEQ ID NO: 2, a heavy-chain CDR3 comprising a sequence set forth in SEQ ID NO: 3, a light-chain CDR1 comprising a sequence set forth in SEQ ID NO: 4, a light-chain CDR2 comprising a sequence set forth in SEQ ID NO: 5 and a light-chain CDR3 comprising a sequence set forth in SEQ ID NO: 6; and
(ii) a pharmaceutical composition comprising a monoclonal antibody to at least one of human PD-1, PD-L1 and PD-L2 or an antigen-binding fragment thereof, capable of disrupting the binding of PD-1 to its ligands.
18. The composition of claim 1 , wherein said monoclonal antibody to human PD-L1 is selected from the group consisting of MEDI-4736, BMS-936559, MSB0010718C, MPDL3280A, antigen-binding fragments thereof, and any combination thereof.