Abstract: In an embodiment of the present invention, compounds of the present application or pharmaceutically acceptable salts thereof are capable of interacting with and activating the stimulator of interferon genes (STING) protein. In an embodiment of the present invention, pharmaceutical compositions and methods involving such compounds as STING modulators are additionally provided herein.

Abstract: Following DNA damage events, such as radiation therapy, cytosolic dsDNA species are generated that trigger intrinsic STimulator of Interferon Genes (STING) signaling and render cells competent for phagocytic activation contingent on the chemokine CCL5 (C-C Motif Ligand 5). Loss of STING signaling or inducible CCL5, rendered DNA-damaged cells incapable of APC stimulation following phagocytosis. STING signaling facilitated the generation of immunogenic endosomal vesicles comprising the autophagy related proteins RAB9 and LC3, and cytosolic DNA which triggered APC activation in trans, an event which also required extrinsic cGAS/STING-dependent signaling. Further, the combination of radiation treatment in the presence of type I IFN greatly reduced tumor growth while rescuing the ability to generate CTL activity. Reconstitution of STING signaling and/or the combination of radiation treatment in the presence of type I IFN could significantly augment cancer therapy.

Abstract: In an embodiment of the present invention, compounds of the present application or pharmaceutically acceptable salts thereof are capable of interacting with and activating the stimulator of interferon genes (STING) protein. In an embodiment of the present invention, pharmaceutical compositions and methods involving such compounds as STING modulators are additionally provided herein.

Abstract: Compounds of the present application or pharmaceutically acceptable salts thereof are capable of interacting with and attenuating the activity of a stimulator of interferon genes (STING) protein. In an embodiment of the invention, inhibitors compounds bind to STING and attenuate STING downstream signaling. Pharmaceutical compositions and methods involving such compounds as STING modulators are additionally provided herein.

Abstract: In an embodiment of the present invention, compounds of the present application or pharmaceutically acceptable salts thereof are capable of interacting with and activating the stimulator of interferon genes (STING) protein. In an embodiment of the present invention, pharmaceutical compositions and methods involving such compounds as STING modulators are additionally provided herein.

Abstract: Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) can be delivered to antigen presenting cells. In various embodiments of the present invention, the STAVs can be delivered in lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers Nano-STAVs into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity. The STAV formulations can be introduced into solid tumors present in the mammal. Alternatively, the Nano-STAVs can be introduced through direct inoculation. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APC's.

Abstract: Compounds of the present application or pharmaceutically acceptable salts thereof are capable of interacting with and attenuating the activity of a stimulator of interferon genes (STING) protein. In an embodiment of the invention, antagonist compounds bind to STING protein and attenuate STING downstream signaling. Pharmaceutical compositions and methods involving such compounds as STING modulators are additionally provided herein.

Abstract: The present disclosure relates, in general, to oligonucleotides that stimulate STING (STimulator of Interferon Genes) activity and increase activity of immune cells. The disclosed STING activators (STAVs) are useful in the treatment of cancer and other immune-mediated conditions.

Abstract: Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) can be delivered to antigen presenting cells. In various embodiments of the present invention, the STAVs can be delivered in lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers Nano-STAVs into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity. The STAV formulations can be introduced into solid tumors present in the mammal. Alternatively, the Nano-STAVs can be introduced through direct inoculation. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APC's.

Abstract: The present disclosure relates, in general, to oligonucleotides that stimulate STING (STimulator of INterferon Genes) activity and increase activity of immune cells. The disclosed STING activators (STAVs) are useful in the treatment of cancer and other immune-mediated conditions.

Abstract: The invention relates to a vector and/or vaccine that can be used for therapeutic and preventive purposes. The virus is based on vesicular stomatitis virus (VSV) with a substituted VSV G (glycoprotein) for HTLV-1 G, referred to as gp62. The vector and/or vaccine further comprise a fusion protein comprising HTLV-1 regulatory proteins (HBZ and TAX) together to make a fusion product (HBZ-TAX) and mutated versions thereof. The vector and/or vaccine do not impede innate immune signaling and generate neutralizing antibodies and CTLs to gp62, HBZ, and TAX.

Abstract: The present disclosure relates, in general, to methods for screening for modulators of IFN? activity using a GLuc/SEAP dual reporter system.

Abstract: The present disclosure relates, in general, to oligonucleotides that stimulate STING (STimulator of INterferon Genes) activity and increase activity of immune cells. The disclosed STING activators (STAVs) are useful in the treatment of cancer and other immune-mediated conditions.

Abstract: Modulators of STING are able to upregulate or down regulate immune responses. Administration of such modulators can be used to treat diseases or other undesirable conditions in a subject either directly or in combination with other agents.

Abstract: In an embodiment of the present invention, compounds of the present application or pharmaceutically acceptable salts thereof are capable of interacting with and activating the stimulator of interferon genes (STING) protein. In an embodiment of the present invention, pharmaceutical compositions and methods involving such compounds as STING modulators are additionally provided herein.

Abstract: The present disclosure provides, in general, a method for selecting a therapy for treating cancer in a human subject and subsequently treating cancer in a subject, which includes isolating a cancer cell from a human subject having cancer, determining the functional activity of the innate immune regulator STimulator of INterferon Genes (STING) or the cellular nucleotidyltransferase, cyclic Guanosine Monophosphate (cGMP)—Adenosine Monophosphate (AMP) Synthase (cyclicGMP-AMP Synthase or cGAS) in the cell, and selecting a therapy for the cancer based on the functional activity of the STING or cGAS in the cell. Also provided, if the functional activity of STING and/or cGAS is determined to be defective in the cell, the therapy selected is one that is effective at killing STING-deficient and/or cGAS-deficient cancer cells, for example a therapy including administering to the subject an oncolytic virus.

Abstract: The present disclosure relates, in general, to recombinant viral vectors that stimulate STING (STimulator of INterferon Genes) activity and increase activity of immune cells.

Abstract: Modulators of STING are able to upregulate or down regulate immune responses. Administration of such modulators can be used to treat diseases or other undesirable conditions in a subject either directly or in combination with other agents.

Abstract: The present disclosure provides, in general, a method for selecting a therapy for treating cancer in a human subject and subsequently treating cancer in a subject, which includes isolating a cancer cell from a human subject having cancer, determining the functional activity of the innate immune regulator STimulator of INterferon Genes (STING) or the cellular nucleotidyltransferase, cyclic Guanosine Monophosphate (cGMP)-Adenosine Monophosphate (AMP) Synthase (cyclicGMP-AMP Synthase or cGAS) in the cell, and selecting a therapy for the cancer based on the functional activity of the STING or cGAS in the cell. Also provided, if the functional activity of STING and/or cGAS is determined to be defective in the cell, the therapy selected is one that is effective at killing STING-deficient and/or cGAS-deficient cancer cells, for example a therapy including administering to the subject an oncolytic virus.

Abstract: The present disclosure provides, in general, a method for selecting a therapy for treating cancer in a human subject and subsequently treating cancer in a subject, which includes isolating a cancer cell from a human subject having cancer, determining the functional activity of STING or cGAS in the cell; and selecting a therapy for the cancer based on the functional activity of the STING or cGAS in the cell. Also provided, if the functional activity of STING and/or cGAS is determined to be defective in the cell, the therapy selected is one that is effective at killing STING-deficient and/or cGAS-deficient cancer cells, e.g., therapy including administering to the subject an oncolytic virus.