Methods for inducing selective apoptosis
AssigneeBaylor College of Medicine
InventorMalcolm K. Brenner
Life of this patent
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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.
Claims36
A method of treating a patient with therapeutic cells, comprising administering a multimeric ligand to a human patient to whom therapeutic cells have been administered, wherein:
- the therapeutic cells comprise modified T cells;
- the therapeutic cells have been transfected or transduced with a nucleic acid comprising (i) a promoter region, and (ii) a polynucleotide that encodes a chimeric protein comprising a multimeric ligand binding region and a caspase 9 polypeptide;
- the promoter region is operatively linked to the polynucleotide;
- the multimeric ligand binding region binds to a multimeric ligand;
- the multimeric ligand binding region comprises a modified FKBP12 polypeptide;
- the modified FKBP12 polypeptide binds with higher affinity to the multimeric ligand than the wild type FKBP12 polypeptide;
- the modified FKBP12 polypeptide comprises an amino acid substitution at position 36;
- activated therapeutic cells are depleted at a rate greater than 90% depletion in one day following administration of the multimeric ligand;
- and
- the activated therapeutic cells are CD3-positive therapeutic cells.
A method of treating a patient with therapeutic cells, comprising administering a multimeric ligand to a human patient to whom therapeutic cells have been administered, wherein:
- the therapeutic cells comprise modified T cells;
- the therapeutic cells have been transfected or transduced with a nucleic acid comprising (i) a promoter region, and (ii) a polynucleotide that encodes a chimeric protein comprising a multimeric ligand binding region and a caspase 9 polypeptide;
- the promoter region is operatively linked to the polynucleotide;
- the multimeric ligand binding region binds to a multimeric ligand;
- the multimeric ligand is AP20187 or AP1903;
- the multimeric ligand binding region comprises a modified FKBP12 polypeptide;
- the modified FKBP12 polypeptide binds with higher affinity to the multimeric ligand than the wild type FKBP12 polypeptide;
- activated therapeutic cells are depleted at a rate greater than 90% depletion in one day following administration of the multimeric ligand:
- and
- the activated therapeutic cells are CD3-positive therapeutic cells.
Dependencies are inferred from the claim text.