Intracellular genomic transplant and methods of therapy
AssigneesIntima Bioscience, Inc., Regents of the University of Minnesota, The United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsBranden Moriarity, Beau Webber, David Largaespada, Modassir Choudhry, Steven A. Rosenberg
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Abstract
Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.
Claims25
A method of genomically modifying a population of human immune cells, the method comprising contacting ex vivo or in vitro the population of human immune cells with:
- a) a polynucleic acid that encodes an exogenous T cell receptor or a chimeric antigen receptor, wherein said exogenous T cell receptor or said chimeric antigen receptor binds a cancer antigen;
- b) a ribonuclear protein complex, wherein the ribonuclear protein complex comprises:
- i) a guide RNA that binds a first gene locus within said human immune cells;
- and
- ii) a Cas protein;
- and
- c) a polynucleic acid that encodes a homologous recombination enhancer,
- wherein the population of human immune cells are synchronized prior to said contacting with the ribonuclear protein complex, wherein the ribonuclear protein complex performs a genomic disruption within a target sequence of the first gene locus that comprises any one of SEQ ID NOS:
- 75-86, thereby generating genomically modified human immune cells, wherein the genomic disruption reduces or eliminates production of a protein encoded by the first gene locus as compared to a comparable human immune cell lacking the genomic disruption in the first gene locus, wherein the homologous recombination enhancer suppresses non-homologous end joining, and wherein said genomically modified human immune cells express said exogenous T cell receptor or chimeric antigen receptor.
A method of genomically modifying a population of human immune cells, the method comprising contacting ex vivo or in vitro the population of human immune cells with:
- a) a polynucleic acid that encodes an exogenous T cell receptor or a chimeric antigen receptor, wherein said exogenous T cell receptor or said chimeric antigen receptor binds a cancer antigen;
- b) a ribonuclear protein complex, wherein the ribonuclear protein complex comprises:
- i) a guide RNA that binds a target sequence of a first gene locus that comprises any one of SEQ ID NOS:
- 75-86, and
- ii) a Cas protein,
- wherein the population of human immune cells are synchronized prior to said contacting with the ribonuclear protein complex, wherein the ribonuclear protein complex performs a genomic disruption within the target sequence, thereby generating genomically modified human immune cells, wherein the genomic disruption reduces or eliminates production of a protein encoded by the first gene locus as compared to a comparable human immune cell lacking the genomic disruption in the first gene locus, and wherein said genomically modified human immune cells express said exogenous T cell receptor or chimeric antigen receptor;
- and
- c) culturing the genomically modified human immune cells in IL-2.
Dependencies are inferred from the claim text.