Methods for inducing selective apoptosis
AssigneeBaylor College of Medicine
InventorMalcolm K. Brenner
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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.
Claims34
A method of controlling the survival of therapeutic cells in a human patient, comprising administering a multimeric ligand to a human patient to whom therapeutic cells have been administered, wherein:
- 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 binds to the multimeric ligand binding region;
- 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 substation at position 36;
- the number of therapeutic cells that express the caspase 9 polypeptide is reduced at least 90% within 24 hours following administration of the multimeric ligand.
A method of controlling the survival of therapeutic cells in a human patient, comprising administering a multimeric ligand to a human patient to whom therapeutic cells have been administered, wherein:
- 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 binds to the multimeric ligand binding region;
- 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;
- and
- the number of therapeutic cells that express the caspase 9 polypeptide is reduced at least 90% within 24 hours following administration of the multimeric ligand.
Dependencies are inferred from the claim text.