Methods for inducing selective apoptosis

Abstract

Provided herein are methods for cell therapy by modifying transfused cells to express an inducible caspase 9 protein, so that the cells may be selectively killed if the patient experiences dangerous side effects. Provided also within relates in part to methods for preventing or treating Graft versus Host Disease by modifying T cells before administration to a patient, so that they may be selectively killed if GvHD develops in the patient.

What is claimed is: 
     
         1 . A cell, comprising a nucleic acid including a promoter region and a nucleotide sequence that encodes a chimeric protein comprising a multimeric ligand binding region and a caspase 9 polypeptide, wherein the cell is obtained or prepared from bone marrow or umbilical cord blood. 
     
     
         2 . The cell of  claim 1 , wherein the cell is selected from the group consisting of mesenchymal stromal cells, embryonic stem cells, and inducible pluripotent stem cells. 
     
     
         3 . The cell of  claim 1 , wherein the cell is a T cell. 
     
     
         4 . The cell of  claim 1 , wherein the caspase 9 polypeptide is a truncated caspase 9 polypeptide. 
     
     
         5 . The method of  claim 1 , wherein the promoter is activated in activated T cells. 
     
     
         6 . The method of  claim 1 , wherein the chimeric protein further comprises a marker polypeptide. 
     
     
         7 . The composition of  claim 1 , wherein the ligand-binding region is selected from the group consisting of FKBP ligand-binding region, cyclophilin receptor ligand-binding region, steroid receptor ligand-binding region, cyclophilin receptor ligand-binding region, and tetracycline receptor ligand-binding region. 
     
     
         8 . The composition of  claim 1 , wherein the ligand-binding region comprises a FV′Fvls amino acid sequence. 
     
     
         9 . The composition of  claim 1 , wherein the ligand is a small molecule. 
     
     
         10 . The composition of  claim 1 , wherein the ligand is dimeric. 
     
     
         11 . The composition of  claim 10 , wherein the ligand is dimeric FK506, or a dimeric FK506 analog.