Mitochondria-enriched genetically engineered cells and uses thereof
AssigneesMinovia Therapeutics Ltd., Tel HaShomer Medical Research Infrastructure and Services Ltd.
InventorsNatalie Yivgi-Ohana, Noa Sher, Moriya Blumkin, Elad Jacoby
Life of this patent
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Abstract
The present invention is based on the discovery that cells enriched with mitochondria are useful for treating diseases and disorders. Disclosed are pharmaceutical compositions of mitochondrially-enriched genetically engineered T cells and methods of treatment using mitochondrially-enriched genetically engineered T cells.
Claims18
A pharmaceutical composition comprising mitochondrially-enriched genetically engineered T cells and a pharmaceutically acceptable carrier, wherein the mitochondrially-enriched genetically engineered T cells are produced by a method comprising:
- a) contacting T cells obtained from a subject afflicted with a disease or disorder or from a donor with exogenous mitochondria at a ratio of about 0.88-4.4 mU citrate synthase (CS) activity per 106 T cells, and introducing a nucleic acid encoding a chimeric T cell receptor (TCR) or chimeric antigen receptor (CAR) into the T cells;
- or
- b) introducing a nucleic acid encoding a chimeric TCR or CAR into T cells obtained from a subject afflicted with a disease or disorder or from a donor, and contacting the T cells with exogenous mitochondria at a ratio of about 0.88-4.4 mU CS activity per 106 T cells,
- wherein the mitochondrial content of the mitochondrially-enriched genetically engineered T cells is at least 1% higher than the mitochondrial content of the T cells prior to contacting the T cells with the exogenous mitochondria, and the method does not comprise reducing mtDNA content of the T cells prior to contacting the T cells with the exogenous mitochondria.
A method of treating a disease or disorder in a subject in need thereof comprising administering to the subject mitochondrially-enriched genetically engineered T cells, wherein the method further comprises the following steps for preparing the mitochondrially-enriched genetically engineered T cells:
- a) contacting T cells obtained from a subject afflicted with a disease or disorder or from a donor with exogenous mitochondria at a ratio of about 0.88-4.4 mU citrate synthase (CS) activity per 106 T cells, and introducing a nucleic acid encoding a chimeric T cell receptor (TCR) or chimeric antigen receptor (CAR) into the T cells;
- or
- b) introducing a nucleic acid encoding a chimeric TCR or CAR into T cells obtained from a subject afflicted with a disease or disorder or a from donor, and contacting the T cells with exogenous mitochondria at a ratio of about 0.88-4.4 mU CS activity per 106 T cells,
- wherein the mitochondrial content of the mitochondrially-enriched genetically engineered T cells is at least 1% higher than the mitochondrial content of the T cells prior to contacting the T cells with the exogenous mitochondria, and the method does not comprise reducing mtDNA content of the T cells prior to contacting the T cells with the exogenous mitochondria.
A method of preparing mitochondrially-enriched genetically engineered T cells, comprising:
- a) contacting T cells obtained from a subject afflicted with a disease or disorder or from a donor with exogenous mitochondria at a ratio of about 0.88-4.4 mU citrate synthase (CS) activity per 106 T cells, and introducing a nucleic acid encoding a chimeric T cell receptor (TCR) or chimeric antigen receptor (CAR) into the T cells;
- or
- b) introducing a nucleic acid encoding a chimeric TCR or CAR into T cells obtained from a subject afflicted with a disease or disorder or from a donor, and contacting the T cells with exogenous mitochondria at a ratio of about 0.88-4.4 mU CS activity per 106 T cells,
- wherein the mitochondrial content of the mitochondrially-enriched genetically engineered T cells is at least 1% higher than the mitochondrial content of the T cells prior to contacting the T cells with the exogenous mitochondria, and the method does not comprise reducing mtDNA content of the T cells prior to contacting the T cells with the exogenous mitochondria.
Dependencies are inferred from the claim text.