28 results about "Interleukin 18" patented technology

Fusion proteins are provided that consist of essential elements such as one or more proteins / polypeptides capable of transporting into the endoplasmic reticulum (ER) and fragments or variants of interleukin 18 (IL-18) or IL-18. The proteins / polypeptides capable of transporting into the ER include, but are not limited to, immune globular proteins (e.g., Fc regions, VHH antibodies, and scFv), and globular proteins (e.g., serum albumin). In some embodiments, the IL-18 may be a pro-IL-18 similar to a natural precursor cytokine, wherein IL-18 is fused to the C-terminus of a propeptide or a propeptide variant thereof. In some embodiments, the fusion protein may further comprise a cleavable peptide linker.

Provided are nucleic acids that encode decoy-resistant interleukin 18 (DR-18) polypeptides, as well as vectors and cells comprising such nucleic acids and cells that comprise such vectors. Cells encoding DR-18 polypeptides may be referred to as DR-18 armored cells. The nucleic acids may further encode a chimeric antigen receptor (CAR) or multiple CARs, including CARs that bind to antigens described herein. Methods are also provided, including methods of making the nucleic acids, vectors, and / or cells, as well as methods of use, such as employing the nucleic acids, vectors, and / or cells, in the treatment of a subject having cancer.

Described herein are method of using fusion proteins composed of elements such as one or more proteins / polypeptides capable of translocating into an endoplasmic reticulum (ER) and an interleukin 18 (IL-18) or a fragment or variant of IL-18. The proteins / polypeptides capable of translocating into the ER include but are not limited to an immunoglobular protein such as Fc region, VHH antibody, and scFv, and a globular protein such as serum albumin. The IL-18 may be a precursor IL-18 that resembles the natural pro-cytokine in which IL-18 is fused to the C-terminus of its propeptide or a propeptide variant. These fusion proteins can be used in methods of treating cancer or fibrosis by activating an IL-18 receptor complex (RC) signal on a cell, releasing or exposing mature IL-18 in a tumor microenvironment or adjacent to a tumor and / or increasing memory CD8+ T cell proliferation.

The present disclosure relates a modified interleukin 18 (IL-18) polypeptide comprising a polymer, methods of making the same, and methods of using the modified IL-18 polypeptides for treatment of diseases including cancer. The modified IL-18 polypeptide can exhibit an half-a maximal effective concentration (EC50) to induce IFNγ production is a cell lower than the EC50 of wild type IL-18 (WT IL-18). The modified IL-18 polypeptide can exhibit superior tumor growth inhibition properties and increased half-life in plasma compared to an identical IL-18 polypeptide with no polymer attached. The modified IL-18 polypeptide can also include an optimally sized polymer attached for enhanced efficacy.

The present disclosure provides multispecific antigen binding proteins that bind to one or more cytokines, more particularly to pro-inflammatory cytokines. In particular, the present disclosure relates to multispecific antigen binding proteins that comprise an interleukin 18 (IL-18) binding domain and an interleukin 23 (IL-23) binding domain, and the use of said multispecific antigen binding proteins in medicine.

Provided are constructs comprising an interleukin 18 (IL-18) component associated with a binding moiety that specifically binds to an antigen. In some cases, the IL-18 component has a decreased binding affinity to an IL-18 receptor as compared to a corresponding wildtype IL-18 polypeptide (e.g., SEQ ID NO: 1). In some cases, a single IL-18 component is associated with a multivalent antibody. Also provided are related nucleic acids, vectors, host cells, methods of producing constructs, pharmaceutical compositions comprising the constructs, and uses of such pharmaceutical compositions.

Provided are interleukin 18 (IL-18) variant polypeptides that comprise mutation(s) at one or more of G3, E6, D54, and N91, wherein amino acid positions are relative to a wild-type human IL-18 set forth in SEQ ID NO: 1. Also provided are IL-18 variant polypeptide comprising (such as further comprising) at least one mutation at a residue selected from the group consisting of: C38, C68, C76, D98, S117, and C127, wherein the amino acid position is relative to a wild-type human IL-18 set forth in SEQ ID NO: 1. Also provided are IL-18 variant polypeptides bind IL-18Rα and exhibit substantially reduced binding to IL-18BP relative to the wild-type IL-18. Also provided are IL-18 variant polypeptides that exhibit increased binding IL-18Rα relative to the wild-type IL-18 and substantially reduced binding to IL-18BP relative to the wild-type IL-18. Also provided are related nucleic acids, vectors, host cells, methods of producing IL-18 variant polypeptides, pharmaceutical compositions comprising IL-18 variant polypeptides, and uses of such pharmaceutical compositions.

The present invention relates to interleukin 18 (IL-18) antibody therapies, low dose formulations of anti-IL-18 neutralizing antibodies, and the use of such formulations for the treatment of IL-18 related diseases by subcutaneous administration. The invention further relates to the use of said anti-IL-18 neutralizing antibody low-dose formulations in the treatment of e.g., adult pathogenic Stetill Disease (AOSD) or systemic pathogenic juvenile idiopathic arthritis (SoJIA, SoJIA, SoJIB, SoJIA, SoJIB, SoJIA, SoJIA, SoJIA, SoJIA, the present invention relates to the use thereof in Still disease such as Still disease (e.g., juvenile Still disease), atopic eczema or atopic dermatitis (AD), inflammatory bowel disease such as ulcerative colitis (UC) and Crohn's disease (CD), and eosinophilic esophagitis (EoE).

The present disclosure provides multispecific antigen binding proteins that bind to one or more cytokines, more particularly to pro-inflammatory cytokines. In particular, the present disclosure relates to multispecific antigen binding proteins that comprise an interleukin 18 (IL-18) binding domain and an interleukin 23 (IL-23) binding domain, and the use of said multispecific antigen binding proteins in medicine.

The present invention addresses the problem of providing an immune cell induced from an iPS cell, which imparts a phenotype that facilitates local migration and infiltration into a solid tumor and proliferation and survival of the immune cell in the solid tumor. [Solution] A cell which is an immune cell induced from an iPS cell and which expresses interleukin 15 and a cell surface molecule that is reactive with a tumor-associated antigen. And a cell which is an immune cell induced from an iPS cell and which expresses a cell surface molecule that is reactive with a tumor-associated antigen and interleukin 12, interleukin 18, or interleukin 21.

Provided herein are variant human IL-18 (hIL-18) proteins and fusion proteins comprising the variant hIL-18 proteins. Such variant hIL-18 proteins exhibit biological IL-18 activity while having reduced or no detectable binding to inhibitory IL-18BP. Thus, in some embodiments, the variant hIL-18 proteins advantageously retain IL-18 biological activity in the presence of IL-18BP. Such variant hIL-18 and related fusion proteins find use, for example, in the treatment of cancer.

Disclosed herein is a method for selecting a subject for bladder cancer therapy based on determining from the sample from a subject with bladder cancer, the presence, absence, or level of a biomarker that correlates with interleukin 18 binding protein (IL-18 BP) expression by bladder cells from a subject. Also disclosed herein are compositions comprising an effective amount of at least one of interleukin 18 (IL-18) and an inhibitor of IL-18 binding protein (IL-18 BP), wherein the inhibitor causes at least one of reduces binding of IL-18 BP to IL-18 and reduces IL-18 BP levels. The compositions may be used in methods for treating bladder cancer, comprising administering to a subject in need thereof an effective amount of at least one of IL-18, an inhibitor of IL-18 BP, an antagonist of an activator of IL-18 BP, and an agonist of a down-regulator of IL-18 BP.

The present invention relates to a method for diagnosing or determining the risk of suffering from Alzheimer's disease in a subject, wherein the method comprises determining the level of at least the biomarkers Neurofilament light Chain (NfL), brain-derived neurotrophic factor (BDNF), and tumor growth factor beta 1 (TGF-beta 1) and in addition determining the level of one or more biomarkers selected from the group comprising interleukin 18 (IL-18), Monocyte chemotactic protein-1 (MCP-1), Insulin-like growth factor (IGF) and Vascular endothelial growth factor (VEGF) in a sample of bodily fluid of said subject, calculating a score from the determined biomarker levels, and comparing said score with a reference score, and wherein said subject is diagnosed with Alzheimer's disease, or said subject is determined as having a risk of suffering from Alzheimer's disease, if the score is above said reference score.

The invention relates to application of a KHDRBS1 gene in preparation of a medicine for regulating secretion of an inflammatory factor IL-18. The KHDRBS1 gene is knocked out or overexpressed to regulate the secretion of interleukin 18, the knockout can promote the secretion of tumor cells and enhance the anti-tumor immune response, and the tumor cells after the KHDRBS1 gene is knocked out can remarkably up-regulate the secretion of IL-18 under the synergistic effect of F1 / F3 polypeptide, so that the immune killing function of NK cells and T cells on tumors is further activated, and the tumor immune killing effect is improved. The tumor growth is effectively inhibited; on the contrary, the overexpression of the KHDRBS1 gene plays an important role in autoimmune diseases. Therefore, the regulation and control effect of the KHDRBS1 in tumor cells and autoimmune diseases is disclosed for the first time, and an important thought and a wide application prospect are provided for developing a new strategy based on KHDRBS1 gene knockout / overexpression and F1 / F3 synergistic immunotherapy.

The invention relates to interleukin 18 (IL-18) antibody therapy, and to low dosage formulations of an anti-IL-18 neutralizing antibody, and their use in treating IL-18-associated diseases via sub-cutaneous delivery. The invention further relates to the use of the low dose formulations of the anti-IL-18 neutralizing antibody for treating Still's diseases, such as adult-onset Still's disease (AOSD) or the juvenile-onset form know as systemic-onset juvenile idiopathic arthritis (SoJIA)), atopic eczema or atopic dermatitis (AD), inflammatory bowel disease, such as ulcerative colitis (UC) and Crohn's disease (CD), and eosinophilic esophagitis (EoE).

The present disclosure relates a modified interleukin 18 (IL-18) polypeptide comprising a polymer, methods of making the same, and methods of using the modified IL-18 polypeptides for treatment of diseases including cancer. The modified IL-18 polypeptide can exhibit an half-a maximal effective concentration (EC50) to induce IFNγ production is a cell lower than the EC50 of wild type IL-18 (WT IL-18). The modified IL-18 polypeptide can exhibit superior tumor growth inhibition properties and increased half-life in plasma compared to an identical IL-18 polypeptide with no polymer attached. The modified IL-18 polypeptide can also include an optimally sized polymer attached for enhanced efficacy.

The present invention provides means and methods for treating Interleukin 18 (IL-18)-associated diseases and disorders. In particular, the present invention discloses antibodies specific for free IL-18 and IL-18 Binding Protein (IL-18BP) for use in such treatments and for the diagnosis of the diseases and disorders.

The present disclosure provides multispecific antigen binding proteins that bind to one or more cytokines, more particularly to pro-inflammatory cytokines. In particular, the present disclosure relates to multispecific antigen binding proteins that comprise an interleukin 18 (IL-18) binding domain and an interleukin 23 (IL-23) binding domain, and the use of said multispecific antigen binding proteins in medicine.

The present disclosure relates to modified interleukin-18 (IL-18) polypeptides, methods for their production, and methods of using the modified IL-18 polypeptides for the treatment of diseases, including cancer. The modified IL-18 polypeptides may exhibit the ability to induce interferon gamma (IFNγ) production when contacted with a cell, may exhibit a reduced ability to be inhibited by IL-18 binding protein (IL-18BP) compared to wild-type IL-18 (WT IL-18), and may exhibit a ratio of half maximal inhibitory concentration (IC50) by IL-18BP to half maximal effective concentration (EC50) for inducing IFNγ production that is greater than that of WT IL-18.

Provided herein are variant human IL-18 (hIL-18) proteins and fusion proteins comprising the variant hIL-18 proteins. Such variant hIL-18 proteins exhibit biological IL-18 activity while having reduced or no detectable binding to inhibitory IL-18BP. Thus, in some embodiments, the variant hIL-18 proteins advantageously retain IL-18 biological activity in the presence of IL-18BP. Such variant hIL-18 and related fusion proteins find use, for example, in the treatment of cancer.

Provided are constructs comprising an interleukin 18 (IL-18) component associated with a binding moiety that specifically binds to an antigen. In some cases, the IL-18 component has a decreased binding affinity to an IL-18 receptor as compared to a corresponding wildtype IL-18 polypeptide (e.g., SEQ ID NO: 1). In some cases, a single IL-18 component is associated with a multivalent antibody. Also provided are related nucleic acids, vectors, host cells, methods of producing constructs, pharmaceutical compositions comprising the constructs, and uses of such pharmaceutical compositions.

Provided are methods, and reagents and kits for performing such methods, directed to treating subjects with cancer, including subjects with hematological cancers and subjects with solid tumors, including subjects with relapsed and / or refractory hematological cancers, subjects with metastatic, recurrent, relapsed, unresectable, and / or advanced tumors. Provided are methods of treating cancer comprising administering a decoy-resistant interleukin 18 (DR-18), including e.g., using combination therapies comprising administering a DR-18 and a multi-specific therapeutic. Methods may also include selecting a patient, and administering a DR-18 to result in enhanced cytotoxic activity of immune cells in the patient to treat the subject for cancer. Also provided are methods for administration of DR-18, to prime immune cells present in the subject, and administration of one or more agents that activate the primed immune cells, resulting in enhanced cytotoxic activity, thereby treating the cancer.

The present invention relates to an hexahydro-s-indacene compound of Formula (I) or its pharmaceutically acceptable salt wherein A is selected from the group consisting of (A1), (A2) and (A3) as defined in the claims. The compounds of the invention are medicaments for use in the treatment of immunopathologies related to the NLRP3 inflammasome, such as for example cancer, metabolic disorders, migraine, wound repair, neurodegenerative diseases and autoimmune diseases. The hexahydro-s-indacene compound of the invention is a selective inhibitor of the activation of the NL-RP3 inflammasome and, as such, is capable of reducing the NLRP3-mediated production of interleukin-1β and interleukin 18 in mammalian cells and tissues.

Applicants have identified biomarkers that can be expressed at elevated levels in subjects who are prone to developing diabetes. The biomarkers can include misfolded proinsulin, correctly folded proinsulin, follistatin, hemoglobin A1c, C-Reactive Protein, Interleukin 18 and Interleukin 1 Receptor Antagonist, glutamic decarboxylase autoantibodies, islet cell autoantibodies, insulin autoantibodies, zinc transporter protein autoantibodies, insulinoma associated-2 autoantibodies, C-reactive protein, protectin D1, a lipoxin and a maresin. Embodiments include methods of predicting or assessing a subject's risk of developing diabetes before onset of the disease. The methods can also determine the progression and / or prognosis of diabetes. A subject who is at risk of developing the disease can be any of Type 1, Type 1.5 or Type 2 diabetes.

The present disclosure relates a modified interleukin 18 (IL-18) polypeptide comprising a polymer, methods of making the same, and methods of using the modified IL-18 polypeptides for treatment of diseases including cancer. The modified IL-18 polypeptide can exhibit an half-a maximal effective concentration (EC50) to induce IFNγ production is a cell lower than the EC50 of wild type IL-18 (WT IL-18). The modified IL-18 polypeptide can exhibit superior tumor growth inhibition properties and increased half-life in plasma compared to an identical IL-18 polypeptide with no polymer attached. The modified IL-18 polypeptide can also include an optimally sized polymer attached for enhanced efficacy.

Provided herein are variant human IL-18 (hIL-18) proteins and fusion proteins comprising the variant hIL-18 proteins. Such variant hIL-18 proteins exhibit biological IL-18 activity while having reduced or no detectable binding to inhibitory IL-18BP. Thus, in some embodiments, the variant hIL-18 proteins advantageously retain IL-18 biological activity in the presence of IL-18BP. Such variant hIL-18 and related fusion proteins find use, for example, in the treatment of cancer.

The invention relates to the technical field of synthetic biology, in particular to nucleic acid for coding human interleukin 18 and application of the nucleic acid in tobacco expression. The invention provides a coding nucleic acid of human IL-18, and provides an expression cassette, a plasmid vector, a transformant and a method for expressing IL-18. The scheme at least has one of the beneficial effects that the technical blank of plant source IL-18 production is filled; the optimized nucleic acid enables a larger amount of IL-18 to be expressed in the tobacco body.

Described herein are methods of using fusion proteins consisting of elements such as one or more proteins / polypeptides capable of translocation into the endoplasmic reticulum (ER) and fragments or variants of interleukin 18 (IL-18) or IL-18. Proteins / polypeptides capable of translocation into the ER include, but are not limited to, immunoglobulins such as Fc regions, VHH antibodies and scFvs, and globular proteins such as serum albumin. IL-18 can be a precursor IL-18 similar to a native procytokine, wherein IL-18 is fused to the C-terminus of its propeptide or propeptide variant. These fusion proteins are useful in methods of treating cancer or fibrosis by activating IL-18 receptor complex (RC) signaling on a cell, releasing or exposing mature IL-18 in or adjacent to a tumor, and / or increasing memory CD8-T cell proliferation.