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US 10,166,255 B2Granted
Intracellular genomic transplant and methods of therapy
AssigneesRegents of the University of Minnesota, Intima Bioscience, Inc., The United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsBranden Moriarity, Beau Webber, R. Scott McIvor, Modassir Choudhry, Steven A. Rosenberg, Douglas C. Palmer, Nicholas P. Restifo
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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.
Claims31
A method of making an engineered population of primary cells comprising:
- a) introducing into a population of primary cells a ribonucleic acid encoding for at least a portion of an exogenous functional T cell receptor sequence or encoding for at least a portion of an exogenous functional chimeric antigen receptor sequence;
- b) reverse transcribing said ribonucleic acid, thereby producing a deoxyribonucleic acid encoding for said at least a portion of an exogenous functional T cell receptor sequence or said at least a portion of an exogenous functional chimeric antigen receptor sequence;
- and
- c) introducing said deoxyribonucleic acid into a genomic break comprising at least a portion of a cytokine inducible SH2-containing protein (CISH) gene in a genome of at least one cell in said population of primary cells, wherein said genomic break is performed by an endonuclease and partially reduces or completely suppresses expression of said CISH gene.
1 more element
A method of making an engineered cell comprising:
- a) introducing a genomic break in a cytokine inducible SH2-containing protein gene in a genome of said cell, wherein said genomic break is introduced by an endonuclease;
- b) introducing into said cell a deoxyribonucleic acid encoding a construct comprising:
- (I) at least a portion of an exogenous functional T cell receptor sequence, or
- (II) at least a portion of an exogenous functional chimeric antigen receptor sequence,
- and at least one homology arm, wherein said at least one homology arm binds to a nucleic acid sequence adjacent to a genomic break at:
- (i) said cytokine inducible SH2-containing protein gene;
- or
- (ii) a T cell receptor alpha gene or a T cell receptor beta gene in a genome of said cell;
- such that said exogenous functional T cell receptor sequence or said exogenous functional chimeric antigen receptor sequence is introduced at said genomic break.
6 more elements
Dependencies are inferred from the claim text.