The ubiquitin ligase, RNF5, regulates the gut microbiota composition and influences the immune checkpoint response to tumors. RNF5 deficient animals exhibit significant inhibition of tumor development as well as an altered gut microbiota composition. Methods of treating cancer by administering to a subject one or more selected bacterial species and/or one or more prebiotics that promote the growth of one or more selected bacterial species are disclosed. Also disclosed are methods of treating cancer by administering to a subject one or more selected bacterial species and/or one or more prebiotics that promote the growth of one or more selected bacterial species in combination with one or more anti-cancer agents.

Provided is a method of activating immune cells and/or an immune system response in a subject. The method may comprise administering to a subject an effective amount of a compound of Formula (I): or a prodrug, derivative, and/or salt thereof. In some embodiments, the method comprises contacting an immune cell with a compound of Formula (I) or a prodrug, derivative, and/or salt thereof. Also provided are compounds, compositions, and kits for activating immune cells and/or an immune system response in a subject. ##STR00001##

Provided is a method of activating immune cells and/or an immune system response in a subject. The method may comprise administering to a subject an effective amount of a compound of Formula (I): or a prodrug, derivative, and/or salt thereof. In some embodiments, the method comprises contacting an immune cell with a compound of Formula (I) or a prodrug, derivative, and/or salt thereof. Also provided are compounds, compositions, and kits for activating immune cells and/or an immune system response in a subject. ##STR00001##

The present disclosure provides an innate immunity cell such as a gamma delta T (gdT) cell, Natural Killer (NK) cell, or macrophage having 2-[3-(1,3-dicarboxypropyl)ureido] pentanedioic acid (DUPA) chemically conjugated to the cell surface. The DUPA-conjugated cells provided herein demonstrate increased cytotoxicity toward cancer cells expressing PSMA. DUPA-conjugated cells can be primary cells or cells of a cell line. Also provided are methods of conjugating DUPA to the surface of NK cells, gamma delta T (gdT) cells, or macrophages and methods of treating cancer using DUPA-conjugated NK cells, gamma delta T (gdT) cells, or macrophages.

The present disclosure provides an innate immunity cell such as a gamma delta T (gdT) cell, Natural Killer (NK) cell, or macrophage having 2-[3-(1,3-dicarboxypropyl)ureido] pentanedioic acid (DUPA) chemically conjugated to the cell surface. The DUPA-conjugated cells provided herein demonstrate increased cytotoxicity toward cancer cells expressing PSMA. DUPA-conjugated cells can be primary cells or cells of a cell line. Also provided are methods of conjugating DUPA to the surface of NK cells, gamma delta T (gdT) cells, or macrophages and methods of treating cancer using DUPA-conjugated NK cells, gamma delta T (gdT) cells, or macrophages.

The invention features methods for the treatment of cystinosis and other cysteamine sensitive disorders in a subject including administration of a disulfide convertible to cysteamine in vivo. The methods can include the separate administration of a reducing agent to the subject to increase the bioavailablity and extend the plasma pharmacokinetic profile of the cysteamine produced following administration of the disulfide. The methods permit sustained cysteamine plasma concentrations in a subject.

The invention features methods for the treatment of cystinosis and other cysteamine sensitive disorders in a subject including administration of a disulfide convertible to cysteamine in vivo. The methods can include the separate administration of a reducing agent to the subject to increase the bioavailablity and extend the plasma pharmacokinetic profile of the cysteamine produced following administration of the disulfide. The methods permit sustained cysteamine plasma concentrations in a subject.

The present disclosure relates to small molecule or polymer conjugated MetAP2 inhibitors. The present disclosure also relates to methods of treating, or ameliorating at least one symptom of metabolic dysfunction associated with a treatment in a subject having a disease, such as cancer. The present disclosure also relates to methods of treating, or ameliorating at least one symptom of cancer comprising administering a combination of a polymer conjugated MetAP2 inhibitors and at least one second agent wherein the second agent may induce metabolic dysfunction.

The present disclosure relates to small molecule or polymer conjugated MetAP2 inhibitors. The present disclosure also relates to methods of treating, or ameliorating at least one symptom of metabolic dysfunction associated with a treatment in a subject having a disease, such as cancer. The present disclosure also relates to methods of treating, or ameliorating at least one symptom of cancer comprising administering a combination of a polymer conjugated MetAP2 inhibitors and at least one second agent wherein the second agent may induce metabolic dysfunction.

Methods for treating an ear condition in a subject, comprising topically administering to the ear of the subject in need thereof a composition comprising: (i) an anti-infective agent-loaded biodegradable polymer microspheres; and (ii) a thermoresponsive hydrogel.