Use of anti-α5β1 antibodies to inhibit cancer cell proliferation
View Patent ↗The present invention provides methods for direct killing of cancer cells using anti-α5β1 antibodies. Generally, the method comprises contacting a cancer cell that expresses α5β1 on its surface with an anti-α5β1 antibody, and thereby inducing the death of the cancer cell. The methods of the invention may be employed at an early stage of cancer development in a patient to prevent tumor establishment. In addition, the methods may be used to treat previously formed tumors especially in cancer that have not proven susceptible to anti-angiogenesis therapy. The methods may be employed as a combination therapy of anti-α5β1 antibodies together with cancer chemotherapeutic agents or other molecular-based cancer therapeutic agents.
1. A pharmaceutical composition comprising a liquid formulation comprising:
about 1.0 mg/mL to 15 mg/mL anti-α5β1 antibody;
about 22 mM to 27 mM citrate;
about 145 mM to 165 mM sodium chloride;
about 0.04% to 0.06% polysorbate-80;
and a pH of about 5.5 to 7.5.
2. The pharmaceutical composition of claim 1 , wherein the concentration of anti-α5β1 antibody is about 10 mg/mL.
3. The pharmaceutical composition of claim 1 , wherein the anti-α5β1 antibody comprises a heavy chain variable sequence of SEQ ID NO: 6 and a light chain variable sequence of SEQ ID NO: 8.
4. The pharmaceutical composition of claim 3 , wherein the anti-α5β1 antibody comprises a Fab fragment of the antibody of claim 3 .
5. The pharmaceutical composition of claim 1 , wherein the composition further comprises a chemotherapeutic agent.
6. The pharmaceutical composition of claim 3 , wherein the pH is about 6.3-6.7.
7. The pharmaceutical composition of claim 1 , wherein the antibody comprises CDR sequences present in the antibody comprising a heavy chain variable sequence of SEQ ID NO: 2 and a light chain variable sequence of SEQ ID NO: 4 and a human IgG constant region.
8. The pharmaceutical composition of claim 7 , wherein the human IgG constant region is IgG4.
9. A pharmaceutical composition comprising a liquid formulation comprising:
about 10 mg/mL anti-α5β1 antibody;
about 25 mM citrate;
about 150 mM sodium chloride;
about 0.05% polysorbate-80;
and a pH of about 6.5.
10. The pharmaceutical composition of claim 9 , wherein the antibody comprises CDR sequences present in the antibody comprising a heavy chain variable sequence of SEQ ID NO: 6 and a light chain variable sequence of SEQ ID NO: 8 and a human IgG constant region.
11. The pharmaceutical composition of claim 10 , wherein the human IgG constant region is IgG4.
12. The pharmaceutical composition of claim 11 , wherein the anti-α5β1 antibody comprises a heavy chain variable sequence of SEQ ID NO: 6 and a light chain variable sequence of SEQ ID NO: 8.
13. A pharmaceutical composition comprising a liquid formulation comprising:
about 10 mg/mL anti-α5β1 antibody;
about 22 mM to 27 mM citrate;
about 145 mM to 165 mM sodium chloride;
about 0.04% to 0.06% polysorbate-80;
and a pH of about 6.5.