Tumor infiltrating lymphocytes 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 Office of Technology Transfer, National Institutes of Health
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 tumor infiltrating lymphocytes, for the treatment of gastrointestinal cancer are disclosed. Disclosed are methods of utilizing a CRISPR system to generate genetically modified compositions. Also disclosed are the methods of making and using the genetically modified compositions for the treatment of gastrointestinal cancer.
Claims33
A method of treating cancer in a human subject in need thereof, comprising:
- (a) administering a lymphodepleting preparative regimen that comprises an immunosuppressant in an amount sufficient to result in lymphodepletion in said human subject;
- (b) administering a pharmaceutical composition that comprises an antifungal agent in an amount sufficient to inhibit a fungal infection in said human subject;
- and
- (c) administering a pharmaceutical composition that comprises a plurality of tumor infiltrating lymphocytes (TILs), wherein said TILs comprise CD4+ T cells, wherein said CD4+ T cells comprise a genomic disruption of at least a portion of a cytokine inducible SH2-containing protein (CISH) gene, and wherein said genomic disruption suppresses or eliminates expression of a CISH protein encoded by said CISH gene thereby treating said cancer.
A method of treating cancer in a human subject in need thereof, comprising:
- a) i) administering a pharmaceutical composition that comprises cyclophosphamide in an amount sufficient to reduce an immune response in said human subject and administering a pharmaceutical composition that comprises fludarabine in an amount sufficient to reduce an immune response in said human subject;
- or ii) administering a pharmaceutical composition that comprises cyclophosphamide and fludarabine in an amount sufficient to reduce an immune response in said human subject;
- b) administering a pharmaceutical composition that comprises fluconazole in an amount sufficient to inhibit a fungal infection in said human subject;
- and
- c) administering a pharmaceutical composition that comprises a plurality of tumor infiltrating lymphocytes (TILs), wherein said TILs comprise CD4+ T cells, wherein said CD4+ T cells comprise a genomic disruption of at least a portion of a cytokine inducible SH2-containing protein (CISH) gene, and wherein said genomic disruption suppresses or eliminates expression of a CISH protein encoded by said CISH gene, thereby treating said cancer.
Dependencies are inferred from the claim text.