Methods for inducing partial apoptosis using caspase polypeptides
AssigneeBellicum Pharmaceuticals, Inc.
InventorsKevin Slawin, David Michael 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.
Claims25
A method of controlling survival of transplanted T cells in a subject, comprising administering a multimeric ligand to a human subject to whom T cells have been administered, wherein the T cells have been transduced or transfected with:
- a) a first nucleic acid that encodes a chimeric polypeptide comprising a multimerization region and a caspase-9 polypeptide or a modified caspase-9 polypeptide, wherein the caspase-9 polypeptide or the modified caspase-9 polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:
- 9;
- and
- b) a second nucleic acid that encodes a chimeric antigen receptor;
- wherein the multimeric ligand binds to the multimerization region in an amount effective to kill less than 80% of transplanted T cells that express the caspase-9 polypeptide or the modified caspase-9 polypeptide;
- and
- wherein at least 1×106 transduced or transfected T cells are administered to the subject.
A method for treating cancer, wherein the method comprises administering T cells to a human subject in need of treatment of said cancer and administering a multimeric ligand to the human subject to control the survival of the T cells, wherein the T cells have been transduced or transfected with:
- a) a first nucleic acid that encodes a chimeric protein comprising a multimerization region and a caspase-9 polypeptide, and
- b) a second nucleic acid that encodes a chimeric antigen receptor,
- wherein the multimeric ligand binds to the multimerization binding region of the chimeric protein, wherein the caspase-9 polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:
- 9, wherein at least 1×106 transduced or transfected T cells are administered to the subject, wherein said method induces partial apoptosis of the T cells in the subject that express the caspase-9 polypeptide, and wherein less than 80% of the T cells in the subject that express the caspase-9 polypeptide are killed following administration of the multimeric ligand.
Dependencies are inferred from the claim text.