Abstract: IL-7R??c binding compounds and pharmaceutical compositions comprising the IL-7R??c binding compounds are disclosed. IL-7R??c bonding compounds can act as IL-7R agonists and are useful in treating cancer, viral diseases, autoimmune diseases, and inflammatory diseases.

Abstract: The invention provides compositions and methods of treating cancer in a patient with a combination therapy comprising a fusion protein of SEQ ID NO: 1 in combination with an immune checkpoint inhibitor. Preferably the patient has failed to achieve complete or partial response with prior or ongoing treatment with an immune checkpoint inhibitor.

Abstract: A CD19-OR-CD20 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD19-OR-CD20 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD19-OR-CD20 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.

Abstract: Provided herein are an interleukin-2 polypeptide and a fusion protein thereof. Also provided herein are their pharmaceutical compositions and methods of use for treating, preventing, or ameliorating one or more symptoms of a proliferative disease.

Abstract: An exosome-based skincare product containing exosomes excreted by lab cultured human umbilical mesenchymal stem cells within a solvent. Most frequently the solvent is a mixture of water and glycerin. Optional ingredients such as skin-conditioning agents, antioxidants, surfactants, buffering agents, viscosity decreasing agents, viscosity increasing agents, peptides, binders, and/or humectants may be included.

Abstract: The present disclosure provides a polypeptide and method for treating and/or preventing nephrotic syndrome, such as but not limited to those associated with minimal change disease and membranous nephropathy, and conditions related to nephrotic syndrome, such as but not limited to, proteinuria and edema, as well as diabetic nephropathy, diabetes mellitus, lupus nephritis or primary glomerular disease. The present disclosure further provides methods for reducing proteinuria and other disease states as discussed herein. Such methods comprise the therapeutic delivery of an Angptl4 polypeptide or Angptl4 polypeptide derivative to a subject.

Abstract: Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

Abstract: The present disclosure provides methods for re-stimulating TIL populations that lead to improved phenotype and increased metabolic health of the TILs and provides methods of assaying for TIL populations to determine suitability for more efficacious infusion after restimulation.

Abstract: The ?c-family cytokines, Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-7 (IL-7), Interleukin-9 (IL-9), Interleukin-15 (IL-15), and Interleukin-21 (IL-21), are associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of ?c-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Peptide and/or peptide derivative antagonists based on the consensus ?c-subunit binding site to inhibit ?c-cytokine activity are described. Also described are peptide and/or peptide derivative antagonists exhibiting Simul-Block activity, and inhibiting the activity of multiple ?c-cytokine family members.

Abstract: Embodiments are directed to methods and compositions for modulating an immune response. In certain aspects the immune response is a type I hypersensitivity response. In particular aspects the subject has allergic asthma or allergic rhinitis. Using a conventional experimental asthma mouse model (BALB/c), the inventors demonstrate that aerosol administration of TLR agonists, in particular a combination of TLR2/6 and TLR9 agonist (e.g., TLR9 oligonucleotide agonist/PAM2CSK4) along with an antigen (e.g., ovalbumin (OVA)) suppresses the immune response as exemplified by the production of antigen-specific IgE and decreases the number of airway eosinophils in bronchoalveolar lavage fluid (BAL) in response to intraperitoneal (IP) immunization with an antigen mixed with alum.

Abstract: The present disclosure provides chimeric antigen receptors, compostions, and methods thereof. In one embodiment the present disclosure provides a method of treating autoimmune diseases, asthma, and preventing or mediating organ rejection in a subject.

Abstract: Antibody variants having decreased or increased ability to mediate CDC due to modifications at the C-terminus of their heavy chains are described. Methods of generating such antibodies, as well as nucleotide constructs and host cells suitable for the production of said antibodies are also described.

Abstract: The present invention relates to immune-stimulating IL-2 fusion proteins comprising antibodies joined to human interleukin-2 (hIL-2). The invention more specifically relates to humanized monoclonal antibodies or fragments thereof joined to hIL-2 or variants thereof and displaying a unique capability of preferentially stimulating cytotoxic T cells and NK cells compared to Treg cells. Furthermore, the invention relates to in vitro and in vivo therapeutic applications of the IL-2 fusion proteins, in particular as an immunotherapy in the treatment of cancer.

Abstract: Provided herein are isolated DNA vectors comprising a heterologous gene, wherein the DNA vector is devoid of bacterial plasmid DNA and/or bacterial signatures, which can abrogate persistence in vivo. The invention also features pharmaceutical compositions (non-immunogenic pharmaceutical compositions) including the DNA vectors of the invention, which can be used for induction of long-term, episomal expression of a heterologous gene in a subject. The invention involves methods of treating a subject by administering the DNA vectors of the invention, including methods of treating disorders associated with a defect in a target gene.

Abstract: The present invention relates, in part, to chimeric proteins that bind a non-cellular structure and their use as therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the chimeric proteins and their use in the treatment of various diseases.

Abstract: The invention is directed to roles for PARP-1 in disease.

Abstract: A method of treating cancer is provided. The method includes administering to a subject in need thereof an effective amount of a compound selected from the group consisting of a glycogen phosphorylase inhibitor, a glycogen synthase inhibitor, a glycogen degradation molecule, an anti-sense oligonucleotide that down-regulates glycogen synthesis, and combinations thereof, where the cancer includes elevated levels of glycogen.

Abstract: The present invention is related to novel methods for identifying a population of subjects that are at risk for developing of atopic allergic diseases, such as atopic dermatitis, and to the prevention and treatment of these allergic diseases.

Abstract: Immune compositions comprising (i) a respiratory syncytial virus (RSV) G polypeptide, which may be a modified G polypeptide relative to the wild-type counterpart, or a nucleic acid encoding such, and (ii) a solvent and one or more immune regulators, wherein the immune regulator(s) is dissolvable in the solvent. Also provided herein are methods for eliciting anti-RSV immune responses using the immune compositions disclosed herein and methods for producing the immune compositions.

Abstract: Provided herein are methods of treating a peripheral nerve injury in a subject. The methods include administering to the subject at or near the site of the peripheral nerve injury an effective amount of a composition comprising an agent that promotes remyelination of the peripheral nerve. Also provided are methods of determining whether a peripheral nerve injury has a capacity for recovery. The methods include selecting a subject with a peripheral nerve injury, administering to the subject a first dose of a composition comprising and agent that promote remyelination and detecting after the first dose one or more characteristics of peripheral nerve recovery, the presence of one or more characteristics of peripheral nerve recovery indicating a peripheral nerve injury has a capacity for recovery and the absence of characteristics of peripheral nerve recovery indicating a peripheral nerve injury without a capacity for recovery.

Abstract: The present invention provides novel IL-12 Fc fusion proteins, methods of making and using the same. The IL-12 Fc fusion proteins are useful for treatment of cancer and can be used in combination with checkpoint blockade.

Abstract: The invention relates to a composition comprising regulatory T (Treg) cells or effector T cells (Teff) which stably express an interleukin selected from the group consisting of interleukin-2 (IL-2) or interleukin-15 (IL-15).

Abstract: Recombinant interleukin-11 (rhIL-11) is expressed in yeast, then isolated from aerobic fermentation media by precipitation, solubilization of the precipitate in the presence of a denaturant, and renaturation of the solubilized protein. Renatured rhIL-11 is further purified by cation exchange and hydrophobic interaction chromatography to provide a highly purified rhIL-11 with high biological activity and low rhIL-11 dimer and oxidized rhIL-11 content.

Abstract: Ex vivo determination of increased tumor immunogenicity of a tumor biopsy is used as a guide to identify immunotherapy of a tumor in a patient. Most preferably, the ex vivo tests will include exposure of biopsy samples to stress conditions to produce pretreated tumor cells that are then assayed with immune competent cells for increased activation or activity. Test conditions include exposure of the biopsy samples to immune stimulatory compositions, antibodies against neoepitopes, and/or modified cells, and an increase of immunogenicity is preferably determined by their exposure to T cells and/or NK cells.

Abstract: Methods and compositions for treating Gaucher disease are described.

Abstract: Combination therapeutics for the treatment of cancer include the use of immune effector cells, IL-15 based superagonists and one or more immunotherapeutic agents such as Bacillus Calmette-Guerin (BCG).

Abstract: Aspects of the invention provide methods for harnessing the potential of proteins that occur naturally (e.g., in humans) and that have serious but finite toxicity. Aspects of the invention relate to a quantitative systems-biological and structural approach to design a class Mof chimeric proteins that avoid the toxicity of protein drugs while retaining their desired activities. In particular, chimeric proteins containing a variant form of a natural protein fused to a targeting moiety may be administered to a subject to target a signal (e.g., induction of apoptosis) to particular cells without having a generalized toxic effect.

Abstract: The disclosure provides interleukin 37 (IL-37) fusion proteins, methods of making IL-37 fusion proteins including constructs used to express IL-37 fusion proteins, and methods of using IL-37 fusion proteins. In some embodiments, the IL-37 fusion protein includes amino acids 46-206 of isoform B of IL-37 and a heavy chain portion of an antibody.

Abstract: Use of a naturally glycosylated polyphenol, not containing nitrogen, as protective agent against the effects of ultraviolet irradiation on photo-degradable substances of structures.

Abstract: The invention provides hydrogel, wherein the hydrogel has a supramolecular cross-linked network obtainable or obtained from the complexation of an aqueous composition including a host, such as cucurbituril, and one or more polymers having suitable guest functionality. One or more polymers in the aqueous composition may have a molecular weight of 50 kDa or more, such as 200 kDa or more. The hydrogel may hold a component, such as a therapeutic compound or a biological molecule. The hydrogels are suitable for use in medicine.

Abstract: The present disclosures related to human interleukin-2 (hIL2) muteins, pharmaceutical formulations thereof, methods for preparing interleukin-2 muteins, recombinant vectors and cells comprising nucleic acids encoding IL2 muteins and methods for the treatment of human disease.

Abstract: The disclosure relates to compounds and methods of treatment relating to nicotinic receptor antagonists. For example, the compounds and methods of treatment function block the activity of certain acetylcholine receptors and subtypes therein, and are useful treating diseases and conditions mediated by nicotinic receptor stimulation, e.g., diabetes mellitus, chronic kidney disease, acute kidney failure, and reduction of blood glucose levels.

Abstract: This application provides an immunity-inducing agent comprising, as an active ingredient, at least one polypeptide having immunity-inducing activity and selected from (a) polypeptides consisting of amino acid sequences represented by SEQ ID NO: 8, 4, 6, 10, 12, 2 and 14, and polypeptides consisting of 7 or more consecutive amino acids in the amino acid sequences, (b) polypeptides having a sequence identity of 85% or more with the amino acid sequences represented by SEQ ID NO: 8, 4, 6, 10, 12, 2 and 14, and polypeptides consisting of 7 or more consecutive amino acids in the amino acid sequences, and (c) polypeptides comprising the polypeptides according to (a) or (b) as the partial sequences, or a recombinant vector comprising a polynucleotide encoding the polypeptide and capable of expressing the polypeptide in vivo.

Abstract: The present invention discloses a novel therapeutic intervention for osteoporosis. The present invention discloses that Interleukin-3 (IL-3) can be utilized as a therapeutic intervention against osteoporosis and for regulating bone homeostasis. The present invention also provides a method for determining the pre-disposition of a subject for osteoporosis by measuring the RANKL/OPG level.

Abstract: The present disclosure provides compositions and methods for improving reproductive health of mammals and increasing milk production from female mammals. The methods involve administering an effective amount of IL-8 to a female mammal such that the reproductive health of the mammal is improved, or milk production from the mammal is increased, or the fat content of the milk is increased, or the dry matter intake of the mammal is improved, or a combination thereof occurs. In another aspect the disclosure includes prophylaxis and/or therapy of uterine conditions by administering IL-8 to a female mammal. The disclosure includes but is not necessarily limited to systemic administration of the IL-8. Kits for carrying out the methods are also included.

Abstract: A bone biospecific agent comprises a contrast material core, which is visible using Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). The contrast material core is surrounded by a polymeric shell, which is functionalised with a bone-targeting peptide. In use, the peptide targets the biospecific agent to bone. The bone biospecific agent can be used in diagnostic imaging techniques, such as MRI and CT, and in imaging bone remodelling activities, detecting and treating pathological bone conditions and/or bone repair processes. The invention extends to the diagnosis and/or treatment of bone disease and bone pathologies using the biospecific agents.

Abstract: Compositions and methods of making isolated binding molecules (e.g. an antibodies) or antigen-binding fragment thereof useful as therapeutics for treating and/or preventing diseases associated with cells expressing claudin18.2, including tumor-related diseases such as gastric cancer, esophageal cancer, pancreatic cancer, lung cancer, ovarian cancer, colon cancer, hepatic cancer, head-neck cancer, and cancer of the gallbladder are described. Also, described are pharmaceutical formulations comprising the described compositions for the treatment of diseases either as single agent (e.g., naked antibodies) or as adjuvant therapy with other antigen-binding anticancer agents such as immune checkpoint inhibitors (e.g., anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies), and/or by combination therapies where the anti-claudin18.2 antibodies are administered before, after, or concurrently with chemotherapy.

Abstract: Provided are a method for diagnosing cancer, a diagnosis kit and compositions useful for measurement of NK cell activity. The incidence of cancer may be diagnosed by monitoring changes in the in vivo immune system through measurement of NK cell activity in blood. Thus, the incidence of cancer may be readily predicted as described herein using a blood sample from a subject.

Abstract: The present invention relates to 1-acyl-lysophosphatidyl derivatives of general formula I; in which R is C4 to C30 aliphatic hydrocarbyl chain, R1 is selected from H or C1 to C10 alkyl, preferably C1 to C6 alkyl, R2 is selected from H, C10 to C30 acyl or C1 to C10 alkyl, preferably C1 to C6 alkyl, and R3, when present, is selected from H or C1 to C10 alkyl, preferably C1 to C6 alkyl. These derivatives are intended for the treatment of cancer, in particular melanoma, hepatocarcinoma or GIT carcinomas.

Abstract: The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (Treg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound Treg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.

Abstract: The present invention generally relates to immunoconjugates, particularly immunoconjugates comprising a mutant interleukin-2 polypeptide and an antibody that binds to PD-1. In addition, the invention relates to polynucleotide molecules encoding the immunoconjugates, and vectors and host cells comprising such polynucleotide molecules. The invention further relates to methods for producing the mutant immunoconjugates, pharmaceutical compositions comprising the same, and uses thereof.

Abstract: The present disclosure provides compositions and methods for improving reproductive health of mammals and increasing milk production from female mammals. The methods involve administering an effective amount of IL-8 to a female mammal such that the reproductive health of the mammal is improved, or milk production from the mammal is increased, or the fat content of the milk is increased. In another aspect the disclosure includes prophylaxis and/or therapy of uterine conditions by administering IL-8 to a female mammal.

Abstract: The present invention relates to a human CD123-targeting chimeric receptor ligand, comprising an IL-3 molecule-based CD123 binding domain, a transmembrane region, and an intracellular signaling domain. The present invention provides a T cell modified by the human CD123-targeting chimeric receptor ligand and capable of specifically binding with CD123 on tumor cell surfaces, thereby having specific cytotoxicity on tumor cells. The present invention further relates to an application of the human CD123-targeting chimeric receptor ligand and an immune effector cell thereof in preparing an anti-tumor immunotherapy drug.

Abstract: Disclosed herein is a bi-specific antibody that specifically directs a therapeutic agent to a cancer cell by targeting a tumor antigen of the cancer cell, and thereby suppressing the growth of the cancer or blocking the invasion or metastasis of the cancer. The bi-specific antibody of the present disclosure includes a first antigen binding site that binds to polyethylene glycol (PEG); and a second antigen binding site that binds to a target ligand, such as a tumor antigen.

Abstract: A nucleic acid construct and an immune cell, which harbor nucleic acids encoding a CAR and nucleic acids encoding at least one anti-inflammatory or immunosuppressant protein and methods of using the same in treatment or amelioration of inflammation or immune-mediated autoimmunity are described.

Abstract: The disclosure provides methods of treating a malignancy comprising administering an effective dose of a chimeric receptor (e.g., CAR or TCR) genetically modified T cell immunotherapy. Some aspects of the disclosure relate to methods of determining an effective dose of a T cell immunotherapy comprising polyfunctional T cells prior to administration to the patient.

Abstract: The inventions relate to the use of hemichannel blockers to modulate cytokine levels in a subject, including the angiogenic cytokine, VEGF, and their production, secretion and/or release, and to the use of hemichannel blockers to reduce or level cytokine activity, including in conditions characterized in whole or in part by angiogenesis and/or vessel leak.

Abstract: The present invention relates to lipid particles comprising at least one cationic lipid, at least one water-soluble therapeutically effective compound and RNA. Further, the present invention relates to a pharmaceutical composition comprising such particles. Said pharmaceutical composition is useful for inducing an immune response. It is also useful in a prophylactic and/or therapeutic treatment of a disease involving an antigen. Furthermore, the present invention relates to a method for producing the particles.

Abstract: The description provides compositions and methods for treating ETBR-related cancer. In certain aspects, the description provides a delivery system for the controlled, systemic release of at least one of ETBR antagonists, caspase-8 inhibitors, or a combination thereof, optionally including an ETAR antagonist, an anti-PD-1 antibody, a bRAF inhibitor, niacinamide or a combination thereof. The compositions described are useful for the treatment of certain cancers, including, e.g., breast cancer, malignant melanoma, squamous cell carcinoma, glioblastoma, as well as others. In addition, the description provides a delivery system for the controlled release of at least one of ETBR antagonists, caspase-8 inhibitors or a combination thereof, optionally including at least one of an ETAR antagonist, an anti-PD-1 antibody, a bRAF inhibitor, niacinamide, or a combination thereof, to the central nervous system that are useful for treating cancers that have spread to the brain.

Abstract: The present invention relates to the unexpected discovery of novel hydrogel formulations that allow for the encapsulation and delivery of living cells and/or drugs to a subject in need thereof. In certain embodiments, the hydrogel compositions of the invention comprise bound bioactive molecules that promote long-term cell viability and allows for the development of vasculature. The invention further provides methods of delivering viable cells and/or drugs to a subject comprising administering the compositions of the invention to the subject in need thereof.