Enhanced reconstitution and autoreconstitution of the hematopoietic compartment
The present disclosure relates to the acceleration of hematopoietic compartment reconstitution in a subject in need of hematopoietic stem cell transplantation by administering a composition having a protein transduction domain-MYC (PTD-MYC) fusion protein in combination with hematopoietic stem cell transplantation and to the enhancement of hematopoietic compartment autoreconstitution in a subject in need thereof by administering a composition having a protein transduction domain-MYC (PTD-MYC) fusion protein.
1. A method of enhancing hematopoietic compartment reconstitution in a subject suffering from a decrease in the amount of endogenous hematopoietic stem cells comprising:
administering a therapeutically effective amount of a composition comprising a MYC-composition, a Bcl-2-composition, or both, to a subject suffering from a decrease in the amount of endogenous hematopoietic stem cells, wherein the MYC composition and the Bcl-2 composition each comprises a protein transduction domain (PTD), and wherein hematopoietic compartment reconstitution is enhanced compared to hematopoietic compartment reconstitution in a subject that is not administered the composition.
2. The method of claim 1 , wherein the decrease in the amount of endogenous hematopoietic stem cells is due to bone marrow failure syndrome.
3. The method of claim 1 , wherein the decrease in the amount of endogenous hematopoietic stem cells is due to chemotherapy or radiation therapy.
4. The method of claim 1 , wherein the subject has cancer.
5. The method of claim 1 , wherein the subject has a hematological malignancy, a myeloma, multiple myeloma, a leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, a lymphoma, indolent lymphoma, non-Hodgkin lymphoma, diffuse B cell lymphoma, follicular lymphoma, mantle cell lymphoma, T cell lymphoma, Hodgkin lymphoma, a neuroblastoma, a retinoblastoma, Shwachman Diamond syndrome, a brain tumor, Ewing's Sarcoma, a Desmoplastic small round cell tumor, a relapsed germ cell tumor, a hematological disorder, a hemoglobinopathy, an autoimmune disorder, juvenile idiopathic arthritis, systemic lupus erythematosus, severe combined immunodeficiency, congenital neutropenia with defective stem cells, severe aplastic anemia, a sickle-cell disease, a myelodysplasia syndrome, chronic granulomatous disease, a metabolic disorder, Hurler syndrome, Gaucher disease, osteopetrosis, malignant infantile osteopetrosis, heart disease, HIV, or AIDS.
6. The method of claim 1 , wherein the subject has received an organ transplant.
7. The method of claim 1 , wherein the subject has received a hematopoietic stem cell (HSC) transplant.
8. The method of claim 7 , wherein the HSC transplant is autologous HSC transplant or an allogenic HSC transplant.
9. The method of claim 1 , wherein the subject has received a myeloablative HSC transplantation procedure.
10. The method of claim 1 , wherein the subject has received a non-myeloablative HSC transplantation procedure.
11. The method of claim 1 , wherein the MYC-composition is a PTD-MYC fusion protein.
12. The method of claim 11 , wherein the MYC-composition is a TAT-MYC fusion protein.
13. The method of claim 1 , further comprising administering a therapeutically effective amount of a second composition comprising hematopoietic stem cells (HSCs) to achieve hematopoietic compartment reconstitution in the subject.
14. The method of claim 13 , wherein the composition comprising a MYC-composition is administered before, after, or concurrently with the administering of the second composition.
15. The method of claim 13 , wherein the composition comprising a MYC-composition is administered at least 1 day after the administering of the second composition.
16. The method of claim 13 , wherein the second composition comprising HSCs was cultured in the presence of a MYC-composition, a Bcl-2-composition, or both before the administering of the second composition.
17. The method of claim 13 , wherein the second composition comprises conditionally immortalized hematopoietic stem cells (HSCs).
18. The method of claim 1 , wherein the enhanced hematopoietic compartment autoreconstitution in the subject results in enhanced T cell compartment autoreconstitution, enhanced B cell compartment autoreconstitution, enhanced NK-cell compartment autoreconstitution, enhanced myeloid cell compartment autoreconstitution, or neutrophil recovery.
19. The method of claim 1 , wherein hematopoietic compartment reconstitution is accelerated compared to hematopoietic compartment reconstitution in a subject that is not administered the composition.
20. The method of claim 19 , wherein administering the composition comprising a MYC-composition, a Bcl-2-composition, or both achieves an at least 50% acceleration in hematopoietic compartment reconstitution compared to hematopoietic compartment reconstitution in a subject that is not administered the composition.