Enhanced reconstitution and autoreconstitution of the hematopoietic compartment

Abstract

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 .- 159 . (canceled) 
     
     
         160 . A method for preventing a decrease in hematopoietic compartment cells in a subject in need thereof, the method comprising administering a composition comprising a PTD-MYC fusion protein to the subject. 
     
     
         161 . The method of  claim 160 , wherein the hematopoietic compartment cells comprise hematopoietic stem cells. 
     
     
         162 . The method of  claim 160 , wherein the decrease in hematopoietic compartment cells is due to chemotherapy or radiation therapy. 
     
     
         163 . The method of  claim 162 , wherein the composition is to be administered prior to chemotherapy or radiation therapy. 
     
     
         164 . The method of  claim 163 , wherein the composition is to be administered about 24 hours prior to the chemotherapy or radiation therapy. 
     
     
         165 . The method of  claim 163 , wherein the composition is to be administered about 48 hours prior to the chemotherapy or radiation therapy. 
     
     
         166 . The method of  claim 162 , wherein the composition is to be administered prior to and following the chemotherapy or radiation therapy. 
     
     
         167 . The method of  claim 166 , wherein the composition is to be administered about 24 hours following chemotherapy or radiation therapy. 
     
     
         168 . The method of  claim 161 , wherein the decrease in hematopoietic compartment cells is due to a bone marrow failure syndrome. 
     
     
         169 . The method of  claim 168 , wherein the bone marrow failure syndrome is aplastic anemia or Gulf War syndrome. 
     
     
         170 . The method of  claim 168 , wherein the bone marrow failure syndrome is an inherited bone marrow failure syndrome (IBMFS). 
     
     
         171 . The method of  claim 170 , the IBMFS is selected from amegakaryocytic thrombocytopenia, Diamond-Blackfan anemia, dyskeratosis congenita, fanconi anemia, Pearson syndrome, severe congenital neutropenia, Shwachman Diamond syndrome, and thrombocytopenia absent radii, IVIC syndrome, WT syndrome, radio-ulnar synostosis, and ataxia pancytopenia. 
     
     
         172 . The method of  claim 161 , wherein the composition prevents a decrease in the endogenous HSCs. 
     
     
         173 . The method of  claim 161 , wherein the PTD-MYC fusion protein is a TAT-MYC fusion protein. 
     
     
         174 . The method of  claim 161 , wherein the PTD-MYC fusion protein is to be administered at a dose of at least 0.1 mg/kg, at least 0.2 mg/kg, at least 0.3 mg/kg, at least 0.4 mg/kg, at least 0.5 mg/kg, at least 0.6 mg/kg, at least 0.7 mg/kg, at least 0.8 mg/kg, at least 0.9 mg/kg, at least 1 mg/kg, at least 2 mg/kg, at least 3 mg/kg, at least 4 mg/kg, at least 5 mg/kg, at least 6 mg/kg, at least 7 mg/kg, at least 8 mg/kg, at least 9 mg/kg, at least 10 mg/kg, at least 20 mg/kg, at least 30 mg/kg, at least 40 mg/kg, or at least 50 mg/kg of the subject's weight. 
     
     
         175 . The method of  claim 161 , wherein the subject has cancer. 
     
     
         176 . The method of  claim 161 , 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. 
     
     
         177 . The method of  claim 161 , wherein the subject is a human subject. 
     
     
         178 . A method of accelerating hematopoietic compartment reconstitution after hematopoietic stem cell (HSC) transplantation in a subject, the method comprising:
 a) administering a therapeutically effective amount of a first composition comprising HSCs to achieve hematopoietic compartment reconstitution in a subject in need thereof; and   b) administering a second composition comprising a PTD-MYC fusion protein to the subject,   wherein administering the second composition achieves an acceleration in hematopoietic compartment reconstitution compared to hematopoietic compartment reconstitution in a subject that is not administered the second composition.   
     
     
         179 . The method of  claim 178 , wherein the a PTD-MYC fusion protein is a TAT-MYC fusion protein.