Methods for inducing partial apoptosis using caspase polypeptides
AssigneeBellicum Pharmaceuticals, Inc.
InventorsKevin Slawin, David Spencer, Aaron Edward Foster
Life of this patent
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Abstract
The technology relates in part to methods for inducing partial apoptosis of cells that express an inducible caspase polypeptide. The technology further relates in part to methods for inducing partial apoptosis of cells that express an inducible modified caspase polypeptide, having a modified dose response curve to the multimeric ligand inducer. The technology also relates in part to methods for cell therapy using cells that express the inducible caspase polypeptide or the inducible modified caspase polypeptide, where the proportion of caspase polypeptide-expressing cells eliminated by apoptosis is related to the administered amount of the multimeric ligand inducer.
Claims57
A method of controlling survival of transplanted therapeutic cells in a subject, comprising:
- a) preparing or obtaining therapeutic cells;
- b) transfecting or transducing the therapeutic cells with a nucleic acid that encodes a chimeric polypeptide comprising a multimerization region and a modified caspase-9 polypeptide, wherein the modified caspase-9 polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:
- 9;
- c) transplanting the transduced or transfected therapeutic cells into the subject;
- and
- d) after (c), administering to the subject a multimeric ligand that binds to the multimerization region in an amount effective to kill less than 50% of transplanted therapeutic cells that express the modified caspase-9 polypeptide wherein a therapeutically effective level of therapeutic cells remain active in the subject following administration of the multimeric ligand;
- wherein the modified caspase-9 polypeptide has a reduced IC50 and an elongated dose response curve in response to the multimeric ligand compared to a caspase-9 polypeptide that is not modified.
A method of controlling survival of transplanted therapeutic cells in a subject, comprising:
- a) preparing or obtaining therapeutic cells;
- b) transfecting or transducing the therapeutic cells with a nucleic acid that encodes a chimeric polypeptide comprising a multimerization region and a caspase-9 polypeptide, wherein the caspase-9 polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:
- 9;
- c) transplanting the transduced or transfected therapeutic cells into the subject;
- and
- d) after (c), administering to the subject a multimeric ligand that binds to the multimerization region in an amount effective to kill less than 50% of transplanted therapeutic cells that express the caspase-9 polypeptide wherein a therapeutically effective level of therapeutic cells remain active in the subject following administration of the multimeric ligand.
Dependencies are inferred from the claim text.