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.
Claims24
A method of administering transduced or transfected non-allodepleted allogeneic donor T cells to a human patient, comprising
- a) administering transduced or transfected allogeneic donor T cells to the human patient, wherein:
- the donor T cells have been transduced or transfected 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, wherein the promoter region is operatively linked to the polynucleotide and the multimeric ligand binding region comprises a FKBP12 polypeptide comprising a valine at position 36;
- and
- the donor T cells are not allodepleted from the donor cell culture before transfection or transduction;
- and
- b) administering a multimeric ligand that binds to the multimeric binding region to the patient, wherein:
- the patient exhibits graft versus host disease symptoms wherein alloreactive donor T cells are present following a), and
- the number of alloreactive donor T cells is reduced at least 90% within 24 hours following administration of the multimeric ligand.
A method of treating graft versus host disease, comprising administering a multimeric ligand that binds to a multimeric ligand binding region to a human patient who has undergone allogeneic cell therapy using non-allodepleted donor T cells, wherein
- a) allogeneic donor T cells introduced for the therapy express a chimeric protein comprising
- (i) a multimeric ligand binding region comprising a FKBP polypeptide comprising a valine at position 36;
- and
- (ii) a caspase-9 polypeptide;
- b) following the allogeneic cell therapy, the patient exhibits graft versus host disease symptoms wherein alloreactive donor T cells are present;
- and
- c) the number of alloreactive donor T cells is reduced at least 90% within 24 hours following administration of the multimeric ligand.
A method of administering transduced or transfected non-allodepleted allogeneic donor T cells to a human patient, comprising
- a) administering transduced or transfected allogeneic donor T cells to the human patient, wherein:
- the donor T cells have been transduced or transfected 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, wherein the promoter region is operatively linked to the polynucleotide and the muitimeric ligand binding region comprises a FKBP12 polypeptide comprising a valine at position 36;
- and
- the donor T cells are not allodepleted from the donor cell culture before transfection or transduction;
- and
- b) administering AP1903 to the patient, wherein:
- the patient exhibits graft versus host disease symptoms wherein alloreactive donor T cells are present following a), and
- the number of alloreactive donor T cells is reduced at least 90% within 24 hours following administration of AP1903.
Dependencies are inferred from the claim text.