Back to results
US 11,642,375 B2Granted
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, Modassir Choudhry, Steven A. Rosenberg, Douglas C. Palmer, Nicholas P. Restifo
Life of this patent
Estimating the term…
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
An isolated genetically modified human T cell that comprises:
- a genomic disruption within a cytokine inducible SH2-containing protein gene target sequence that comprises any one of SEQ ID NOS:
- 75-86, wherein said genomic disruption comprises an endonuclease-mediated indel;
- and at least one of:
- i) a complementary DNA, wherein said complementary DNA comprises a homology arm that binds to a nucleic acid sequence adjacent to a genomic disruption in:
- a T Cell Receptor Alpha Constant gene sequence, a T Cell Receptor Beta Locus gene sequence;
- or said cytokine inducible SH2-containing protein gene sequence, and wherein said complementary DNA encodes an exogenous functional T cell receptor, or functional fragment thereof, or an exogenous functional chimeric antigen receptor, or functional fragment thereof;
- or
- ii) a mRNA that when reverse transcribed comprises a homology arm that binds to a nucleic acid sequence adjacent to a genomic disruption in:
- a T Cell Receptor Alpha Constant gene sequence, a T Cell Receptor Beta Locus gene sequence, or said cytokine inducible SH2-containing protein gene sequence, and wherein said mRNA encodes an exogenous functional T cell receptor, or functional fragment thereof, or an exogenous functional chimeric antigen receptor, or functional fragment thereof,
- wherein said exogenous functional T cell receptor, or functional fragment thereof, or said exogenous functional chimeric antigen receptor, or functional fragment thereof, binds a neoantigen.
7 more elements
An isolated genetically modified human T cell that comprises:
- a genomic disruption within a cytokine inducible SH2-containing protein gene target sequence that comprises any one of SEQ ID NOS:
- 75-86, wherein said genomic disruption comprises an endonuclease-mediated indel;
- and at least one of:
- i) a complementary DNA, wherein said complementary DNA comprises a homology arm that binds to a nucleic acid sequence adjacent to a genomic disruption in a T Cell Receptor Alpha Constant-gene sequence, a T Cell Receptor Beta Locus gene sequence, or said cytokine inducible SH2-containing protein gene sequence, and wherein said complementary DNA encodes an exogenous functional receptor capable of binding a cancer cell, or functional fragment thereof;
- or
- ii) a mRNA that when reverse transcribed comprises a homology arm that binds to a nucleic acid sequence adjacent to a genomic disruption in a T Cell Receptor Alpha Constant gene sequence, a T Cell Receptor Beta Locus gene sequence, or said cytokine inducible SH2-containing protein gene sequence, and wherein said mRNA encodes an exogenous functional receptor capable of binding a cancer cell, or functional fragment thereof.
3 more elements
An isolated genetically modified human dendritic cell, B cell, or natural killer cell that comprises:
- a genomic disruption within a cytokine inducible SH2-containing protein gene target sequence that comprises any one of SEQ ID NOS:
- 75-86, wherein said genomic disruption comprises an endonuclease-mediated indel;
- and at least one of:
- (i) a complementary DNA, wherein said complementary DNA comprises a homology arm that binds to a nucleic acid sequence adjacent to a genomic disruption in a T Cell Receptor Alpha Constant-gene sequence, a T Cell Receptor Beta Locus gene sequence, or said cytokine inducible SH2-containing protein gene sequence, and wherein said complementary DNA encodes an exogenous functional receptor capable of binding a cancer cell, or functional fragment thereof;
- or
- ii) a mRNA that when reverse transcribed comprises a homology arm that binds to a nucleic acid sequence adjacent to a genomic disruption in a T Cell Receptor Alpha Constant gene sequence, a T Cell Receptor Beta Locus gene sequence, or said cytokine inducible SH2-containing protein gene sequence, and wherein said mRNA encodes an exogenous functional receptor capable of binding a cancer cell, or functional fragment thereof.
3 more elements
Dependencies are inferred from the claim text.