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US 11,903,966 B2Granted
Intracellular genomic transplant and methods of therapy
AssigneesRegents of the University of Minnesota, Intima Bioscience, Inc., The U.S.A., as represented by the Secretary, Department f Health and Human Services
InventorsBranden Moriarity, Beau Webber, 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.
Claims46
A method of treating a neoantigen expressing cancer in a human subject, the method comprising:
- administering to said human subject an immunosuppressive agent;
- and
- administering to said human subject a population of ex vivo engineered neoantigen targeting human primary cells, wherein said population of ex vivo engineered neoantigen targeting human primary cells comprises CD4+ T cells that comprise:
- a) an endonuclease mediated genomic disruption within exon 2 or exon 3 of a cytokine inducible SH2-containing protein gene (CIS-1) sequence, wherein said endonuclease mediated genomic disruption comprises an indel, and wherein said genomic disruption suppresses expression of a protein encoded by the cytokine inducible SH2-containing protein gene (CIS-1);
- and
- b) an exogenous functional neoantigen targeting T cell receptor polypeptide or functional neoantigen targeting fragment thereof, or an exogenous functional neoantigen targeting chimeric antigen receptor polypeptide or functional neoantigen targeting fragment thereof, wherein said neoantigen is expressed by said neoantigen expressing cancer, and
- wherein said cancer is selected from the group consisting of:
- bladder cancer, bone cancer, brain cancer, breast cancer, esophageal cancer, gastrointestinal cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, anal cancer, rectal cancer, ocular cancer, cancer of the neck, gallbladder cancer, pleural cancer, oral cancer, cancer of the vulva, colon cancer, cervical cancer, fibrosarcoma, kidney cancer, mesothelioma, mastocytoma, nasopharynx cancer, pancreatic cancer, peritoneal cancer, small intestine cancer, stomach cancer, testicular cancer, and thyroid cancer.
5 more elements
A method of treating a cancer in a human subject, the method comprising:
- administering to said human subject an immunosuppressive agent;
- and
- administering to said subject a population of ex vivo engineered cancer targeting human primary cells, wherein said population of ex vivo cancer targeting engineered human primary cells comprises CD4+ T cells that comprise:
- a) an endonuclease mediated genomic disruption within exon 2 or exon 3 of a cytokine inducible SH2-containing protein gene (CIS-1) sequence, wherein said endonuclease mediated genomic disruption comprises an indel, and wherein said genomic disruption suppresses expression of a protein encoded by the cytokine inducible SH2-containing protein gene (CIS-1);
- and
- b) an exogenous cell surface receptor or functional fragment thereof capable of binding a cell of said cancer, and
- wherein said cancer is selected from the group consisting of bladder cancer, bone cancer, brain cancer, esophageal cancer, gastrointestinal cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, anal cancer, rectal cancer, ocular cancer, cancer of the neck, gallbladder cancer, pleural cancer, oral cancer, cancer of the vulva, colon cancer, cervical cancer, fibrosarcoma, kidney cancer, mesothelioma, mastocytoma, nasopharynx cancer, pancreatic cancer, peritoneal cancer, small intestine cancer, stomach cancer, testicular cancer, and thyroid cancer.
4 more elements
A method of treating a neoantigen expressing cancer in a human subject, the method comprising:
- administering to said human subject an immunosuppressive agent;
- and
- administering to said human subject a population of ex vivo engineered neoantigen targeting human primary cells, wherein said population of ex vivo engineered neoantigen targeting human primary cells comprises CD4+ T cells that comprise:
- a) an endonuclease mediated genomic disruption within exon 2 or exon 3 of a cytokine inducible SH2-containing protein gene (CIS-1) sequence, wherein said endonuclease mediated genomic disruption comprises an indel, and wherein said genomic disruption suppresses expression of a protein encoded by the cytokine inducible SH2-containing protein gene (CIS-1);
- and
- b) an exogenous functional neoantigen targeting T cell receptor polypeptide or functional neoantigen targeting fragment thereof, or an exogenous functional neoantigen targeting chimeric antigen receptor polypeptide or functional neoantigen targeting fragment thereof, wherein said neoantigen is expressed by said neoantigen expressing cancer,
- and wherein said cancer is selected from the group consisting of:
- gastrointestinal cancer, breast cancer, and prostate cancer.
5 more elements
Dependencies are inferred from the claim text.