Saposin C-DOPS: a novel anti-tumor agent
Compositions and methods for treating subjects with disorders characterized by hyper-proliferating cells such as tumors and cancers are provided. The compositions comprise agents that are combinations of saposin C (or prosaposin-related polypeptides) and phospholips (or inner leaflet components). This anti-tumor agent is administered in the methods of the invention according to a dosing regimen. Administering an agent of the invention results in a positive therapeutic response in a subject with a tumor.
1. A composition comprising
a phospholipid, wherein the phospholipid is phosphatidylserine;
an isolated saposin C-related polypeptide, wherein the polypeptide has an amino acid sequence at least 85 percent identical to SEQ ID NO: 2 and wherein the polypeptide includes amino acids 24-40 of SEQ ID NO: 2;
wherein the phospholipid forms a nanovesicle embedding the polypeptide; and
wherein the nanovesicle embedding the polypeptide exhibits anti-tumor activity.
2. The composition of claim 1 , wherein the polypeptide has an amino acid sequence at least 90 percent identical to SEQ ID NO: 2.
3. The composition of claim 1 , wherein the polypeptide has an amino acid sequence at least 95 percent identical to SEQ ID NO: 2.
4. The composition of claim 1 , wherein the molar ratio of the polypeptide to the phospholipid is in a range from about 1:1 to about 1:50.
5. The composition of claim 1 , wherein the molar ratio of the polypeptide to the phospholipid is in a range from about 1:1 to about 1:10.
6. The composition of claim 1 , wherein the mass ratio of the polypeptide to the phospholipid is in a range from about 15:1 to about 3:10.
7. The composition of claim 1 , wherein the nanovesicle has a diameter between 0.01 μm to 1 μm.
8. The composition of claim 1 , wherein the nanovesicle has a diameter between 10 nm to 800 nm.
9. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
10. The composition of claim 1 , further comprising an additional active ingredient.
11. A composition comprising
a phospholipid, wherein the phospholipid is phosphatidylserine;
and isolated saposin C-related polypeptide, wherein the polypeptide has an amino acid sequence at least 85 percent identical to SEQ ID NO: 2 and wherein the polypeptide includes amino acids 4-20 of SEQ ID NO:2;
wherein the polypeptide retains plasma-membrane affinity; and
wherein the phospholipid forms a nanovesicle embedding the polypeptide; and
wherein the nanovesicle embedding the polypeptide exhibits anti-tumor activity.
12. The composition of claim 11 , wherein the polypeptide has an amino acid sequence at least 90 percent identical to SEQ ID NO: 2.
13. The composition of claim 11 , wherein the polypeptide has an amino acid sequence at least 95 percent identical to SEQ ID NO: 2.
14. The composition of claim 11 , wherein the molar ratio of the polypeptide to the phospholipid is in a range from about 1:1 to about 1:50.
15. The composition of claim 11 , wherein the molar ratio of the polypeptide to the phospholipid is in a range from about 1:1 to about 1:10.
16. The composition of claim 11 , wherein the mass ratio of the polypeptide to the phospholipid is in a range from about 15:1 to about 3:10.
17. The composition of claim 11 , wherein the nanovesicle has a diameter between 0.01 μm to 1 μm.
18. The composition of claim 11 , wherein the nanovesicle has a diameter between 10 nm to 800 nm.
19. The composition of claim 11 , further comprising a pharmaceutically acceptable carrier.
20. The composition of claim 11 , further comprising an additional active ingredient.