36 results about "Stimulator of interferon genes" patented technology

The present invention provides highly active cyclic-di-nucleotide (CDN) immune stimulators that activate DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the CDNs of the present invention are provided in the form of a composition comprising one or more cyclic purine dinucleotides induce STING-dependent type I interferon production, wherein the cyclic purine dinucleotides present in the composition are substantially pure 2′,5′,2′,5′ and 2′,5′,3′,5′ CDNs, and preferably Rp,Rp stereosiomers thereof.

The present invention provides cyclic-di-nucleotide (CDN) compounds that inhibit signaling at a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the CDNs of the present invention are provided in the form of a composition comprising one or more cyclic purine dinucleotides which inhibit STING-dependent TBK1 activation and the resulting production of type I interferon.

It is an object of the present invention to provide novel and highly active cyclic-di-nucleotide (CDN) immune stimulators that activates DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the CDNs of the present invention are provided in the form of a composition comprising one or more cyclic purine dinucleotides that induce STING-dependent TBK1 activation, wherein the cyclic purine dinuclotides present in the composition are substantially pure Rp,Rp or Rp,Sp stereoisomers, and particularly substantially pure Rp,Rp, or RpSp CDN thiophosphate diastereomers.

The present invention provides a combination therapy which relies on a small molecule immune stimulator—cyclic-di-nucleotide (CDN)—that activates DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes) formulated with allogeneic human tumor cell lines engineered to secrete high amounts of GM-CSF. This combination therapy can provide an ideal synergy of multiple tumor associated antigens, DC recruitment and proliferation, coupled with a potent DC activation stimulus.

Methods and compositions for treating cancer by intratumorally administering a stimulator of interferon genes (STING) agonist are disclosed herein. In some embodiments, there are provided compositions and methods concerning methods for treating cancer in a subject comprising administering to the subject an effective amount of a stimulator of interferon genes (STING) agonist, wherein the STING agonist is administered intratumorally.

A kit of parts includes a) gemcitabine or a pharmaceutically acceptable salt thereof and b) a cyclic dinucleotide or pharmaceutically acceptable salt thereof, wherein the cyclic dinucleotide or pharmaceutically acceptable salt thereof is an agonist of the receptor known as “stimulator of interferon genes” (STING), for use in the treatment of solid pancreatic cancer.

The present invention relates to the use cyclic-di-nucleotide and related scaffold molecules that measurably inhibit STING signaling, and methods for their use in identifying more potent inhibitors of STING signaling. In particular, the methods provided can be used to identify potent inhibitors of STING signaling, which are useful in the treatment of autoimmune and inflammatory diseases. Also provided are compounds having STING inhibitory activity useful in the treatment of autoimmune and inflammatory diseases.

Therapeutic combinations that comprise at least one antagonist of the Programmed Death 1 receptor (PD-1) and at least one cyclic dinucleotide compound that activates the Stimulator of Interferon Genes (STING) pathway are disclosed herein. Also disclosed is the use of such therapeutic combinations for the treatment of cancers.

Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and/or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella or by modification of the genes so that functional flagella are not produced, and/or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellin" and/or pagP'. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine and/or purine auxotrophs. The bacteria optionally are one or more of asct, purl' and msbB'. The immunostimulatory bacteria, such as Salmonella species, are modified to encode proteins that induce type I interferon (IFN) expression, or that are variants thereof that have increased activity to induce type I IFN expression, or that are variants thereof that result in constitutive expression of type I IFN. The bacteria can encode a modified Stimulator of Interferon Genes (STING) protein from a non-human species, that has lower NF-kappaB signaling activity, and, optionally, higher type I IFN pathway signaling activity, compared to human STING. The bacteria preferentially infect immune cells in the tumor microenvironment, or tumor-resident immune cells, and/or induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the immunostimulatory bacteria.

The invention discloses cyclic dinucleotide analogues, a pharmaceutical composition of the analogues and applications of the analogues and the pharmaceutical composition. The cyclic dinucleotide analogs (I), an isomer, prodrug, stable isotope derivative or pharmaceutically acceptable salt of the analogs have a structure shown in the specification. The cyclic dinucleotide analogs provided by the invention can be used as regulators of stimulator of interferon genes (STIG) and related signaling pathways, and can effectively treat and/or alleviate multiple types of diseases, including but not limited to malignant tumors, inflammation, autoimmune diseases and infectious diseases; and in addition, the STING regulators can also be used as vaccine adjuvants.

The invention discloses a pair of specificity real-time fluorogenic quantitative PCR (polymerase chain reaction) primers, namely an upstream primer S1-F and a downstream primer S1-R. Accordingly, the inventor designs and sets up a corresponding kit and a corresponding detection method. It is shown through experiments that the detection method, the primer pair and the kit have the advantages of being high in detection speed, accurate in quantification, high in specificity and sensitivity, good in repeatability and stability and free of pollution. A technological platform is provided for fast and accurately detecting the relative expression level of chicken-original STING (stimulator of interferon genes) mRNA, and a technological base is provided for further inquiring an innate immunity mechanism of chicken-related diseases.

Therapeutic combinations that comprise at least one antagonist of the Programmed Death 1 receptor (PD-1) and at least one benzo[b]thiophene compound that activates the Stimulator of Interferon Genes (STING) pathway are disclosed herein. Also disclosed is the use of such therapeutic combinations for the treatment of cancers.

A vaccine against Mycobacterium tuberculosis (M. tuberculosis) formulated for intranasal administration, comprises a first vaccine component comprising one or more M. tuberculosis, Mycobacterium vaccae (M. vaccae) or Mycobacteroium bovis (M. bovis) antigens, and a second vaccine component comprising a Stimulator of Interferon Genes (STING) activator.

Cyclic dinucleotides are described, which in contrast to their natural congeners carry lipophilic nucleobases and have higher membrane permeability and increased biological activity.

The invention features a composition comprising an immuno-stimulatory compound and a pHLIP® peptide, e.g., an immunostimulatory compound that comprises a cyclic purine dinucleotide, which binds to a stimulator of interferon genes (STING) such as a cGAMP cyclic compound inside a cell.

Compounds of the general formula (I):

The invention provides compounds having STimulator of INterferon Genes (STING) agonistic bioactivity that can be used in the treatment of tumors in patients afflicted therewith. The compounds are of formula (I): as defined herein. Compounds for practice of a method of the invention can be delivered via oral delivery for systemic exposure, as well as delivered intratumorally. Antitumor therapy using a compound of formula (I) can further comprise administration of an effective dose of an immune-checkpoint targeting drug.

The present disclosure provides methods, pharmaceutical compositions, and kits for treating cancer in patients in need thereof. The methods comprise administering to a patient in need a STING (stimulator of interferon genes) agonist, such as Compound No. 14 as defined in the description, or a pharmaceutically acceptable salt thereof, in combination with one or more checkpoint inhibitors. Also provided are medicaments for use in treating cancer.