Methods for treating cancer by achieving therapeutically effective doses of anti-CD47 antibody
Methods are provided for treating a subject with a therapeutic dose of anti-CD47 agent by administering a primer agent prior to administering a therapeutically effective dose of an anti-CD47 agent to the subject.
1. A method for treating acute myeloid leukemia (AML) in a human subject, the method comprising:
(a) administering a sub-therapeutic dose of a soluble CD47-binding SIRPα fragment to the subject, wherein the sub-therapeutic dose is capable of increasing production of reticulocytes; and
(b) administering a therapeutically effective dose of the soluble CD47-binding SIRPα fragment to the subject,
wherein the soluble CD47-binding SIRPα fragment blocks an interaction between CD47 and SIRPα.
2. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose from 0.05 mg/kg to 7.5 mg/kg.
3. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose from 0.05 mg/kg to 5 mg/kg.
4. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose from 0.1 mg/kg to 7.5 mg/kg.
5. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose from 0.1 mg/kg to 5 mg/kg.
6. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose from 1 mg/kg to 7.5 mg/kg.
7. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose from 1 mg/kg to 5 mg/kg.
8. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose of 1 mg/kg.
9. The method according to claim 1 , wherein the therapeutically effective dose is administered at a dose from 10 mg/kg to 40 mg/kg.
10. The method according to claim 1 , wherein the therapeutically effective dose is administered at a dose of 30 mg/kg.
11. The method according to claim 1 , wherein step (b) is performed in a range from 3 days to 21 days after beginning the administering of the sub-therapeutic dose.
12. The method according to claim 1 , wherein the sub-therapeutic dose increases the production of the reticulocytes.
13. The method according to claim 1 , wherein in step (a), the sub-therapeutic dose is determined to be effective by measuring in a blood sample from the human subject at least one of: an increase in an absolute or relative number of reticulocytes, an increase in a level of erythropoietin, and a decrease in a level of hemoglobin levels.
14. The method of claim 13 , wherein a reticulocyte count is at least 400×10 9 reticulocytes per liter (L).
15. The method of claim 1 , wherein step (b) comprises administering the soluble CD47-binding SIRPα fragment in two or more doses of escalating concentration until a therapeutically effective dose is administered.
16. The method according to claim 1 , wherein step (b) comprises administering two or more therapeutically effective doses.
17. A method for treating a hematological cancer in a human subject, the method comprising:
(a) administering a sub-therapeutic dose of a soluble CD47-binding SIRPα fragment to the subject, wherein the sub-therapeutic dose is capable of increasing production of reticulocytes; and
(b) administering a therapeutically effective dose of the soluble CD47-binding SIRPα fragment to the subject,
wherein the soluble CD47-binding SIRPα fragment blocks an interaction between CD47 and SIRPα.
18. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose from 0.05 mg/kg to 7.5 mg/kg.
19. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose from 0.05 mg/kg to 5 mg/kg.
20. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose from 0.1 mg/kg to 7.5 mg/kg.
21. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose from 0.1 mg/kg to 5 mg/kg.
22. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose from 1 mg/kg to 7.5 mg/kg.
23. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose from 1 mg/kg to 5 mg/kg.
24. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose of 1 mg/kg.
25. The method according to claim 17 , wherein the therapeutically effective dose is administered at a dose from 10 mg/kg to 40 mg/kg.
26. The method according to claim 17 , wherein the therapeutically effective dose is administered at a dose of 30 mg/kg.
27. The method according to claim 17 , wherein step (b) is performed in a range from 3 days to 21 days after beginning the administering of the sub-therapeutic dose.
28. The method according to claim 17 , wherein the sub-therapeutic dose increases the production of the reticulocytes.
29. The method according to claim 17 , wherein in step (a), the sub-therapeutic dose is determined to be effective by measuring in a blood sample from the human subject at least one of: an increase in an absolute or relative number of reticulocytes, an increase in a level of erythropoietin, and a decrease in a level of hemoglobin levels.
30. The method of claim 28 , wherein a reticulocyte count is at least 400×10 9 reticulocytes per liter (L).
31. The method of claim 17 , wherein step (b) comprises administering the soluble CD47-binding SIRPα fragment in two or more doses of escalating concentration until a therapeutically effective dose is administered.
32. The method according to claim 17 , wherein step (b) comprises administering two or more therapeutically effective doses.
33. The method according to claim 17 , wherein the hematological cancer is leukemia.
34. The method of claim 31 , wherein the leukemia is acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).