Methods for preventing or treating conditions related to t cell mediated intestinal disorders
AssigneeThe Regents of the University of Michigan
InventorPavan Reddy
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Abstract
Provided herein are compositions and methods for preventing, attenuating or treating T cell mediated intestinal disorders. In particular, provided herein are methods for preventing, attenuating or treating T cell mediated intestinal disorders characterized with reduced intestinal epithelial cell (IEC) specific mitochondrial complex II component intrinsic succinate dehydrogenase A (SDHA) activity and/or expression through use of compositions comprising a therapeutic agent capable of preventing and/or hindering reduction of IEC related SDHA activity and/or expression.
Claims40
A method for treating, ameliorating, or preventing a T cell mediated intestinal disorder in a patient comprising administering to a patient suffering from or at risk of suffering from a T cell mediated intestinal disorder a therapeutically effective amount of a composition comprising a therapeutic agent capable of preventing and/or hindering one or more of reduced IEC related SDHA activity and/or expression;
- reduced IEC related oxidative phosphorylation;
- increased IEC related succinate accumulation;
- and increased IEC related accumulation of perforin dependent granzyme B related to cytotoxic T cell engagement with such IECs.
A method for treating, ameliorating, or preventing a reduction of IEC related SDHA activity and/or expression in a patient comprising administering to a patient a therapeutically effective amount of a composition comprising a therapeutic agent capable of preventing and/or hindering one or more of reduced IEC related SDHA activity and/or expression;
- reduced IEC related oxidative phosphorylation;
- increased IEC related succinate accumulation;
- and increased IEC related accumulation of perforin dependent granzyme B related to cytotoxic T cell engagement with such IECs.
A method for treating, ameliorating, or preventing a reduction of IEC related oxidative phosphorylation in a patient comprising administering to a patient a therapeutically effective amount of a composition comprising a therapeutic agent capable of preventing and/or hindering one or more of reduced IEC related SDHA activity and/or expression;
- reduced IEC related oxidative phosphorylation;
- increased IEC related succinate accumulation;
- and increased IEC related accumulation of perforin dependent granzyme B related to cytotoxic T cell engagement with such IECs.
A method for treating, ameliorating, or preventing an increase of IEC related succinate accumulation in a patient comprising administering to a patient a therapeutically effective amount of a composition comprising a therapeutic agent capable of preventing and/or hindering one or more of reduced IEC related SDHA activity and/or expression;
- reduced IEC related oxidative phosphorylation;
- increased IEC related succinate accumulation;
- and increased IEC related accumulation of perforin dependent granzyme B related to cytotoxic T cell engagement with such IECs.
A method for treating, ameliorating, or preventing an increase of IEC related accumulation of perforin dependent granzyme B related to cytotoxic T cell engagement with such IECs in a patient comprising administering to a patient a therapeutically effective amount of a composition comprising a therapeutic agent capable of preventing and/or hindering one or more of reduced IEC related SDHA activity and/or expression;
- reduced IEC related oxidative phosphorylation;
- increased IEC related succinate accumulation;
- and increased IEC related accumulation of perforin dependent granzyme B related to cytotoxic T cell engagement with such IECs.
A method for reducing or preventing a reduction of IEC related SDHA activity and/or expression in a biological sample comprising exposing to the biological sample a therapeutically effective amount of a composition comprising a therapeutic agent capable of preventing and/or hindering one or more of reduced IEC related SDHA activity and/or expression;
- reduced IEC related oxidative phosphorylation;
- increased IEC related succinate accumulation;
- and increased IEC related accumulation of perforin dependent granzyme B related to cytotoxic T cell engagement with such IECs.
A method for reducing or preventing a reduction of IEC related oxidative phosphorylation in a biological sample comprising exposing to the biological sample a therapeutically effective amount of a composition comprising a therapeutic agent capable of preventing and/or hindering one or more of reduced IEC related SDHA activity and/or expression;
- reduced IEC related oxidative phosphorylation;
- increased IEC related succinate accumulation;
- and increased IEC related accumulation of perforin dependent granzyme B related to cytotoxic T cell engagement with such IECs.
A method for reducing or preventing an increase of IEC related succinate accumulation in a biological sample comprising exposing to the biological sample a therapeutic agent capable of preventing and/or hindering one or more of reduced IEC related SDHA activity and/or expression;
- reduced IEC related oxidative phosphorylation;
- increased IEC related succinate accumulation;
- and increased IEC related accumulation of perforin dependent granzyme B related to cytotoxic T cell engagement with such IECs.
A method for reducing or preventing an increase of IEC related accumulation of perforin dependent granzyme B related to cytotoxic T cell engagement with such IECs in a biological sample comprising exposing to the biological sample a therapeutically effective amount of a composition comprising a therapeutic agent capable of preventing and/or hindering one or more of reduced IEC related SDHA activity and/or expression;
- reduced IEC related oxidative phosphorylation;
- increased IEC related succinate accumulation;
- and increased IEC related accumulation of perforin dependent granzyme B related to cytotoxic T cell engagement with such IECs.
A method for treating, ameliorating, or preventing a cancer characterized by resistance to cancer therapies (e.g., those cancer cells which are chemoresistant, radiation resistant, hormone resistant, and the like) comprising co-administering to a patient suffering from or at risk of suffering from such a cancer 1) a therapeutic agent capable of one or more of inhibiting and/or decreasing IEC related SDHA activity and/or expression;
- inhibiting and/or decreasing IEC related oxidative phosphorylation;
- increasing IEC related succinate accumulation;
- and increasing IEC related accumulation of perforin dependent granzyme B related to cytotoxic T cell engagement with such IECs, and 2) an immune checkpoint inhibitor.
Dependencies are inferred from the claim text.