Compounds of formulae (I) and (II), compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo.

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Compounds of formulae (I) and (II), compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo.

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Methods of treating a subject with cancer with CD8 T cell-mediated immune therapy are provided. The methods include measuring an amount of CXCR3-positive T cells in a peripheral blood sample or a tumor sample from a subject with cancer following treatment of the subject with at least one dose of the CD8 T cell-mediated therapy and comparing the amount of CXCR3-positive T cells in the sample to a control. Responsiveness of the cancer to the CD8 T cell-mediated therapy is predicted based on whether there is an increase or decrease in the amount of CXCR3-positive T cells in the sample. Methods further including treating the subject with at least one additional dose of the CD8 T cell-mediated immune therapy are also provided.

Methods of treating a subject with cancer with CD8 T cell-mediated immune therapy are provided. The methods include measuring an amount of CXCR3-positive T cells in a peripheral blood sample or a tumor sample from a subject with cancer following treatment of the subject with at least one dose of the CD8 T cell-mediated therapy and comparing the amount of CXCR3-positive T cells in the sample to a control. Responsiveness of the cancer to the CD8 T cell-mediated therapy is predicted based on whether there is an increase or decrease in the amount of CXCR3-positive T cells in the sample. Methods further including treating the subject with at least one additional dose of the CD8 T cell-mediated immune therapy are also provided.

Disclosed are compositions engineered nanovesicles and compositions comprising CD38 inhibitors and methods of using said nanovesicles and compositions to treat an inflammatory liver disease as well as in inhibiting, reducing, or repairing tissue damage to a donor organ or tissue during a transplantation procedure. In one aspect, also disclosed are method of preparing a donor organ or tissue for transplant comprising contacting the organ or tissue with the engineered nanovesicle or compositions disclosed herein.

Disclosed are compositions engineered nanovesicles and compositions comprising CD38 inhibitors and methods of using said nanovesicles and compositions to treat an inflammatory liver disease as well as in inhibiting, reducing, or repairing tissue damage to a donor organ or tissue during a transplantation procedure. In one aspect, also disclosed are method of preparing a donor organ or tissue for transplant comprising contacting the organ or tissue with the engineered nanovesicle or compositions disclosed herein.

Described herein are formulations of a somatostatin modulator, methods of making such formulations, and methods of using such formulations in the treatment of conditions, diseases, or disorders that would benefit from modulation of somatostatin activity.

Described herein are formulations of a somatostatin modulator, methods of making such formulations, and methods of using such formulations in the treatment of conditions, diseases, or disorders that would benefit from modulation of somatostatin activity.

Combination therapy methods, compositions and kits Invention relates to combinations comprising: a) a compound of formula (I)

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or a pharmaceutically or veterinary acceptable salt thereof, wherein:
R.sub.1 R.sub.2 and R.sub.3 have particular meaning; and (b) one or more drugs selected from the group consisting of i) a compound of formula (IV), or a pharmaceutically or veterinary acceptable salt thereof,

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wherein R.sub.5 and R.sub.6 have particular meaning, ii) a sphingosine-1-phosphate receptor inhibitor (S1PR modulator), and iii) a Signal transducer and activator of transcription 3 (STAT3) inhibitor. Particular combinations and single pharmaceutical compositions and kits of parts are disclosed. These combinations, single pharmaceutical compositions and kits of parts are for use in the treatment and/or prevention of an inflammatory neurological disease or condition which can result in the destruction or degeneration of axons or myelin in a subject in need thereof

Combination therapy methods, compositions and kits Invention relates to combinations comprising: a) a compound of formula (I)

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or a pharmaceutically or veterinary acceptable salt thereof, wherein:
R.sub.1 R.sub.2 and R.sub.3 have particular meaning; and (b) one or more drugs selected from the group consisting of i) a compound of formula (IV), or a pharmaceutically or veterinary acceptable salt thereof,

##STR00002##

wherein R.sub.5 and R.sub.6 have particular meaning, ii) a sphingosine-1-phosphate receptor inhibitor (S1PR modulator), and iii) a Signal transducer and activator of transcription 3 (STAT3) inhibitor. Particular combinations and single pharmaceutical compositions and kits of parts are disclosed. These combinations, single pharmaceutical compositions and kits of parts are for use in the treatment and/or prevention of an inflammatory neurological disease or condition which can result in the destruction or degeneration of axons or myelin in a subject in need thereof