Method of increasing survival of a human subject having exposure to an acute exposure to non-therapeutic whole body ionization by administering a therapeutically effective dose of IL-12
View Patent ↗The present invention provides methods for increasing survival in a subject, and/or preserving bone marrow function, and/or promoting hematopoietic recovery or restoration. The methods include administering a dose of IL-12 to the subject following an acute exposure to non-therapeutic whole body ionizing radiation. Formulations and kits are also provided.
1. A method for treating a human subject, said method comprising:
administering subcutaneously or intramuscularly at least one therapeutically effective dose of IL-12 to said subject at least about 24 hours following an acute exposure to non-therapeutic whole body ionizing radiation, wherein said dose increases the probability of survival of a subject by at least 10% over that observed with a subject who has not been administered IL-12 and exposed to the same level of radiation.
2. The method of claim 1 , wherein said dose of IL-12 is less than about 100 μg/m2, less than about 75 μg/m2, less than about 15 μg/m2, less than about 12 μg/m2, or less than about 6 μg/m2.
3. The method of claim 1 , wherein said acute exposure to whole body ionizing radiation is the result of a nuclear event.
4. The method of claim 1 , wherein said acute exposure is at least about 3.5 Gy (LD50).
5. The method of claim 1 , wherein said IL-12 is administered between a range of about 24 hours to about 72 hours after said acute radiation exposure.
6. The method of claim 5 , wherein the IL-12 is administered at about 24 hours after said acute radiation exposure.
7. The method of claim 1 , wherein supportive care is given to said subject simultaneously or following the administration of IL-12.
8. The method of claim 7 , wherein supportive care comprises the administration of one or more antibiotics.
9. The method of claim 7 , wherein supportive care comprises administration of one or more hematopoietic growth factors.
10. The method of claim 7 , wherein supportive care comprises the administration of a blood transfusion.
11. The method of claim 1 , wherein said dose of IL-12 is less than about 3 μg/m2, between about 300 ng/m2 and about 2400 ng/m2, or between about 600 ng/m2 and about 1200 ng/m2.
12. The method of claim 11 , wherein IL-12 is administered along with a carrier molecule that reduces the amount of IL-12 lost during administration.
13. The method of claim 12 , wherein the carrier molecule is a protein at a concentration of about 5 times the concentration of IL-12.
14. The method of claim 1 , wherein said intermediate dose of IL-12 is between a range of about 20 μg/m2 and about 75 μg/m2, or between about 22.5 μg/m2 and about 52.5 μg/m2.
15. The method of claim 1 , wherein at least two doses of IL-12 are administered to said subject, wherein the first dose of IL-12 is less than about 100 μg/m2 and is administered within about 24 hours following an acute exposure to non-therapeutic whole body ionizing radiation, and the second dose of IL-12 is less than about 100 μg/m2 and is administered within about 96 hours following said acute exposure to non-therapeutic whole body ionizing radiation.
16. The method of claim 15 , wherein said second dose is administered at least about 24 hours after said first dose.
17. The method of claim 15 , wherein said second dose is less than said first dose.
18. The method of claim 15 , wherein the second dose of IL-12 is administered at least about 72 hours after exposure.
19. The method of claim 1 , wherein the IL-12 is rhuIL-12.
20. The method of claim 1 , wherein the probability of survival of the subject is increased by at least 20%.
21. The method of claim 1 , wherein said acute exposure is 8 Gy or less.
22. The method of claim 1 , wherein the probability of survival of the subject is increased by at least 30%.
23. The method of claim 1 , wherein the probability of survival of the subject is increased by at least 40%.
24. The method of claim 1 , wherein the probability of survival of the subject is increased by at least 50%.
25. The method of claim 1 , further comprising administering fluids, one or more antibiotics, blood or blood component transfusions, one or more growth factors or hematopoietic growth factors, or a combination thereof to the subject.
26. The method of claim 1 , further comprising administering an effective dose of erythropoietin to the subject.