Uses of IL-12 in hematopoiesis
View Patent ↗Methods for enhancing or stimulating hematopoiesis including the step of administering Interleukin-12 (IL-12) to yield hematopoietic recovery in a mammal in need. Preferred methods include the step of administering IL-12 as an adjuvant therapy to alleviate the hematopoietic toxicities associated with one or more treatment regimens used to combat a disease state. Other methods include administering IL-12 to ameliorate various hematopoietic deficiencies. Still other methods are directed to uses of IL-12 for in-vivo proliferation of hematopoietic repopulating cells, hematopoietic progenitor cells and hematopoietic stem cells. Other disclosed methods are directed to uses of IL-12 for bone marrow preservation or recovery.
1. A method for protecting or restoring hematopoiesis or enhancing peripheral blood cell counts in a mammal having at least one solid tumor, wherein the method comprises:
(a) administering a treatment to the mammal, wherein the treatment targets the solid tumor and has an associated hematopoietic toxicity, and wherein the treatment is selected from the group consisting of radiation therapy and a combination of chemotherapy and radiation therapy; and
(b) administering one single therapeutically effective dose of interleukin-12 (IL-12), wherein:
(i) the administration of IL-12 to the mammal reduces the hematopoietic toxicity of the treatment;
(ii) the dose of IL-12 is from 1 ng/kg up to 400 ng/kg;
(iii) IL-12 is administered without the addition of other cytokines;
(iv) IL-12 is administered about 36 hours before the treatment, about 24 hours before the treatment, about 12 hours before the treatment, within 1 hour after the treatment, about 1 hour after the treatment, about 12 hours after the treatment, or about 24 hours after the treatment; and
(v) no additional dose(s) of IL-12 is administered near the time of administration of the treatment.
2. The method of claim 1 , wherein the method results in an increased remission of at least one solid tumor, as compared to the treatment intended to target the disease state alone.
3. The method of claim 1 , wherein the mammal is a human.
4. The method of claim 1 , wherein:
(a) the treatment comprises one or more high dose treatment modalities;
(b) the treatment is administered in a dose dense treatment regimen; or
(c) a combination thereof.
5. The method of claim 1 , wherein the radiation therapy comprises a near-lethal dose of radiation.
6. The method of claim 1 , wherein the radiation therapy comprises a sub-lethal dose of radiation.
7. The method of claim 1 , wherein the treatment comprises chemotherapy and the chemotherapy treatment comprises administration of more than one chemotherapy.
8. The method of claim 1 , wherein the treatment leads to a deficiency in one or more hematopoietic cell types or lineages and the administration of IL-12 ameliorates the deficiency.
9. The method of claim 8 , wherein the deficiency is selected from the group consisting of:
(a) a general deficiency in hematopoiesis in the mammal;
(b) a deficiency in one or more specific hematopoietic cell lineages; or
(c) a combination thereof.
10. The method of claim 9 , wherein the deficiency in one or more specific hematopoietic cell lineages is selected from the group consisting of lymphopenia, myelopenia, leukopenia, neutropenia, erythropenia, megakaryopenia, and any combination thereof.
11. The method of claim 1 , wherein;
(a) the administration of IL-12 results in protection of bone marrow cells from the associated hematopoietic toxicity of the treatment;
(b) the IL-12 administration results in radioprotection of bone marrow cells;
(c) the treatment comprises chemotherapy and administration of IL-12 results in chemoprotection of bone marrow cells; or
(d) any combination thereof.
12. The method of claim 11 , wherein the bone marrow cells comprise hematopoietic repopulating cells, hematopoietic stem cells, hematopoeitic progenitor cells, or any combination thereof.
13. The method of claim 1 , wherein the dose of IL-12 is 200 ng/kg or less than 200 ng/kg.
14. The method of claim 1 , wherein the dose of IL-12 is 100 ng/kg or less than 100 ng/kg.
15. The method of claim 1 , wherein the dose of IL-12 is 10 ng/kg or less than 10 ng/kg.
16. The method of claim 1 , wherein the IL-12 is administered at about 24 hours before radiation.
17. The method of claim 1 , wherein the IL-12 is administered at about 1 hour or more following radiation.
18. The method of claim 1 , wherein the solid tumor is derived from a disease state selected from the group consisting of breast cancer, lung cancer, prostate cancer, ovarian cancer, lymphomas, malignant melanoma, non-small cell lung cancer, carcinoma of the stomach, ovarian carcinoma, breast carcinoma, small cell lung carcinoma, retinoblastoma, testicular carcinoma, glioblastoma, rhabdomyosarcoma, neuroblastoma, and Ewing's sarcoma.
19. A method for protecting or restoring hematopoiesis or enhancing peripheral blood cell counts in a mammal having at least one solid tumor, wherein the method consists essentially of:
(a) administering a treatment to the mammal, wherein the treatment targets the solid tumor and has an associated hematopoietic toxicity, and wherein the treatment is selected from the group consisting of radiation therapy or a combination of chemotherapy and radiation therapy; and
(b) administering one single therapeutically effective dose of interleukin-12 (IL-12), wherein:
(i) the administration of IL-12 to the mammal reduces the hematopoietic toxicity of the treatment,
(ii) the dose of IL-12 is from 1 ng/kg up to 400 ng/kg;
(iii) IL-12 is administered without the addition of other cytokines; and
(iv) IL-12 is administered about 36 hours before the treatment, about 24 hours before the treatment, about 12 hours before the treatment, within 1 hour after the treatment, about 1 hour after the treatment, about 12 hours after the treatment, or about 24 hours after the treatment.