2033results about "Interleukins" patented technology

The invention provides compositions and methods for treating cancer by using immune effector cells (e.g., T cells, NK cells) engineered to conditionally express an agent which enhances the immune effector response of an immune effector cell that expresses a Chimeric Antigen Receptor (CAR). The conditional agents described herein include agents that target a cancer associated antigen, e.g., a CAR, agents that inhibit one or more checkpoint inhibitors of the immune response, and a cytokine.

Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of FcεRIγ. Notably, CAR constructs with an intracellular domain of FcεRIγ had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK / NK-92 cells.

The present disclosure provides lipid nanoparticle compositions comprising a nucleic acid encoding a therapeutic polypeptide. The disclosure also provides novel IL-15 polypeptides, fusion proteins comprising the IL-15 polypeptides, and nucleic acids encoding the IL-15 polypeptides and the fusion proteins.

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.

Disclosed herein are compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

An antigen targeting, anti-CD16A, and immune effector cell activating trifunctional fusion protein has a CD16A binding region that specifically binds to CD16A, a tumor-associated antigen (TAA) binding region that specifically binds to a TAA, an IL-15 / IL-15Ra complex formed by combining IL-15 and IL-15Ra, and an Fc domain. A designed tumor-targeting innate immune cell activation molecule, i.e., an anti-TAA, anti-CD 16A, and cytokine IL 15 trifunctional fusion protein targets NK cells to a tumor by simultaneously binding to a TAA on tumor cells and CD16A on NK cells, so that the NK cells release perforin and granzymes to induce apoptosis and cause tumor cell death. The cytokine IL15 expands and maintains the function of the NK cells, stimulates immune cell proliferation, and changes the immune microenvironment of the tumor.

The invention discloses an anti-human inflammatory factor interleukin 6 monoclonal antibody and an application thereof. When the monoclonal antibody is prepared, an adopted immunogen is a human inflammatory factor interleukin 6 antigen, and an amino acid sequence of the human inflammatory factor interleukin 6 antigen comprises a sequence as shown in SEQ ID NO: 1. A group of monoclonal antibodies specifically combined with antigens is constructed based on the IL-6 antigens. The IL-6 monoclonal antibody has strong binding capacity with an IL-6 antigen in a clinical sample, has no cross reaction with other proteins, has good specificity and affinity compared with a commercial antigen, can be effectively applied to ELISA and a dry-type immunofluorescence method, has good detection linearity, precision, stability and accuracy, and can be widely applied to the field of immunoassay. The antibody can be combined with the antigen to serve as a detection reagent raw material combination, and has clinical detection advantages.

The present disclosure relates to IL12 receptor agonists with improved therapeutic profiles.

Disclosed herein are extracellular vesicles comprising an immunomodulating component. Also provided are methods for producing the extracellular vesicles and methods for using the extracellular vesicles for treating cancer, GvHD, and autoimmune diseases.

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.

The invention relates generally to compositions and methods for purifying the desired species from a mixture of desired heterodimer and contaminating homodimer immunoglobulin variants by modifying the isoelectric point(s) of the individual chains.

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.

The invention belongs to the technical field of biology, and particularly relates to antibacterial peptide based on large yellow croaker CXCL8 protein and application of the antibacterial peptide. The preparation method comprises the following steps: by taking a large yellow croaker CXCL8 protein as a template, intercepting a linear polypeptide of 13 amino acids, and carrying out carboxyl terminal amidation modification, so as to obtain the antibacterial peptide AVV13N, and the amino acid sequence of the antibacterial peptide AVV13N is Ala-Arg-Trp-Val-Arg-Arg-Val-Leu-Lys-Lys-Met-Val-NH2; the antibacterial peptide AVK13N is obtained by interchanging lysine at the 11th site and valine at the 13th site in an amino acid sequence of the antibacterial peptide AVV13N, and the amino acid sequence of the antibacterial peptide AVK13N is Ala-Arg-Trp-Val-Arg-Arg-Val-Leu-Lys-Lys-Val-Met-Lys-NH2. The molecular weights of the antibacterial peptides AVV13N and AVK13N are both 1669.12 Da, the isoelectric points of the antibacterial peptides AVV13N and AVK13N are both 12.44, and the antibacterial peptides AVV13N and AVK13N are both alkaline polypeptides. The antibacterial peptides AVV13N and AVK13N have broad-spectrum bactericidal activity and can be used for specifically killing gram-positive bacteria and gram-negative bacteria. In addition, the antibacterial peptides AVV13N and AVK13N have relatively weak hemolytic activity, relatively low cytotoxicity and good temperature stability, pH value stability and salt ion stability. The antibacterial peptides AVV13N and AVK13N provided by the invention can replace antibiotics and are applied to prevention and treatment of bacterial diseases.

Compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

The invention relates generally to compositions and methods for purifying the desired species from a mixture of desired heterodimer and contaminating homodimer immunoglobulin variants by modifying the isoelectric point(s) of the individual chains.

Provided for herein in several embodiments are immune cell-based (e.g., natural killer (NK) cell) compositions comprising CD19-directed chimeric antigen receptors. In some, embodiments the anti-CD19 binder portion of the CAR is humanized. In several embodiments, the humanized anti-CD19 CAR expressing cells exhibit enhanced expression of the CAR as well as enhanced cytotoxicity and / or persistence. Several embodiments include methods of using of the anti-CD19 CAR expressing immune cells in immunotherapy.

Provided are a recombinant human interleukin-11 mutant, and a conjugate of the mutant conjugated to a chemical molecule and a use thereof. The recombinant human interleukin-11 mutant achieves soluble expression in an Escherichia coli expression system by means of an SUMO sequence tandem fusion method. The conjugate is obtained by the site-specific conjugation of the mutant to the chemical molecule at a mutant amino acid residue in position W147 by means of a covalent bond. The chemical molecule is at least one of polyethylene glycol, an alkanoic acid aliphatic chain, and a hydrophilic high-molecular polymer containing an alkanoic acid aliphatic chain. The conjugate retains the binding capacity to human interleukin-11 receptor A while demonstrating significantly reduced binding capacity to human IL-6 signal transducer receptor. The conjugate shows the ability to block the signaling between human IL-11 and IL-11 RA and between human IL-11 and GP130 either in vivo or in vitro and can be used for the treatment of associated diseases with tissue fibrosis as a clinical manifestation caused by elevated primary or secondary IL-11.

The invention relates to the technical field of biology, in particular to an IL22 mutant as well as a preparation method and application thereof. According to the invention, IL-22 is mutated, and the mutation site is modified with PEG, so that the obtained mutant has good STAT3 / STAT1 preference, the STAT1 signal activation is significantly reduced, and the proinflammatory effect is significantly reduced. In addition, the compound can preferentially act on target organs of intestinal tracts in vivo, and does not easily activate skin cells to generate adverse reactions.

To identify lipid metabolites that control Th17 cell differentiation and lipid biosynthetic enzymes involved therein, and based on that, to provide a screening method for a therapeutic agent for diseases caused by excessive Th17 cell responses.SOLUTION: Provided is 1-oleoyl-lysophosphatidylethanolamine (LPE(1-18:1)) as a lipid metabolic product that controls Th17 cell differentiation. Since LPE(1-18:1) binds to RORγt with high specificity and promotes differentiation into Th17 cells, a candidate compound for a therapeutic agent for diseases caused by excessive Th17 cell responses can be obtained by selecting a compound that inhibits the binding of LPE(1-18:1) to RORγt. Also provided are five lipid metabolic enzymes (Gpam, Gpat3, Lplat1, Pla2g12a, and Scd2) that are responsible for the biosynthesis of LPE(1-18:1) and control Th17 cell differentiation. By selecting a compound that inhibits the activity or expression of these lipid metabolic enzymes, a candidate compound for a therapeutic agent for diseases caused by excessive Th17 cell responses can be obtained.SELECTED DRAWING: None

The invention relates to the technical field of biomedicine, in particular to a fusion protein combining a double-target chimeric antigen receptor with PD-1 and IL-21, and an extracellular domain of the double-target chimeric antigen receptor sequentially comprises any one of the following components from an N terminal to a C terminal: CIgG scFv-MSLN scFv, CIgG scFv-CLDN18.2 scFv, CIgG scFv-MSLN scFv and CIgG scFv-CLDN18.2 scFv; wherein '-' is a connecting peptide; the cell further comprises a hinge region, a transmembrane region and an intracellular signal transduction region; pD-1 scFv and IL-21 are further fused at the N end of the intracellular signal transduction region. According to the invention, two chimeric antigen receptors of double-target combined PD-1 and IL21 fusion proteins are constructed, and through a synergistic anti-tumor strategy, CAR-T cell functions are enhanced, tumor microenvironment (TME) inhibition is overcome, T cell durability is improved, and synergy is realized.

The invention discloses an engineered NK cell and a preparation method thereof. The antitumor activity of the NK cell is enhanced through synergistic modification of a fusion polypeptide and an anti-TIGIT monoclonal antibody. The amino acid sequence of the fusion polypeptide is shown as SEQ ID NO.1. The fusion polypeptide can specifically target tumor cells and activate the proliferation and killing functions of NK cells. And the anti-TIGIT monoclonal antibody further relieves the immunosuppression by blocking a TIGIT-CD155 signal channel. In-vitro experiments show that the killing rate of the combined modified NK cell on various solid tumors is obviously higher than that of the traditional CAR-NK cell. A PDX model shows that the engineered NK cells significantly inhibit tumor growth and enhance NK cell infiltration in a tumor microenvironment. The invention provides a new strategy with high efficiency and low toxicity for immunotherapy of solid tumors.

The present invention relates to antibody-cytokine conjugates, wherein the cytokine is conjugated to the antibody via a cleavable linker. Conjugates according to the invention can be prepared by coupling a functionalized antibody Ab (F) x comprising x reactive moieties F, where x is an integer in the range of 1-10, with an immune cell-binding polypeptide comprising one or two reactive moieties Q, where the antibody is specific for tumor cells, and the immune cell-binding polypeptide is specific for immune cells, wherein the reaction forms a covalent bond between the functionalized antibody and the immune cell-binding polypeptide by reaction of Q with F. The invention further relates to antibody-cytokine conjugates obtainable by the method according to the invention and to medical uses thereof.

The invention relates to proximity activated cytokine compounds comprising a PD-1 targeting moiety, and an IL-21 polypeptide covalently linked to an anti-IL-21 antibody-binding domain, which together provide targeted cytokine signaling to PD-1 expressing cells. The invention further relates to nucleic acid and expression vectors encoding proximity activated cytokines, as well as use of such compounds for treating cancer.

There is provided an interleukin-21 (IL-21) variant, wherein in comparison to wild-type IL-21 that comprises an amino acid sequence according to SEQ ID NO: 6 or an amino acid sequence comprising at least 70% sequence identity to SEQ ID NO: 6, the IL-21 variant comprises an amino acid modification at one or more of the following amino acid positions: 29, 33, 36 and / or 71.

Provided herein are chimeric antigen receptors (CARs) for cancer therapy, and more particularly, CARs containing a scFv from an anti-ROR-1 monoclonal antibody. Provided are immune effector cells containing such CARs, and methods of treating proliferative disorders.

The present invention provides, in certain aspects, a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15), and methods for producing such cells. The invention further provides methods of using a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15) to treat cancer in a subject or to enhance expansion and / or survival of NK cells.

The present disclosure provides a population of CD4IL-10 / CAR cells (autologous or allogeneic single-donor and allogeneic polydonor) generated by genetically modifying CD4+ Tcells to express IL-10 and a chimeric antigen receptor. Further provided are methods of generating the CD4IL-10 / CAR cells and methods of using the CD4IL-10 / CAR cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, and autoimmune and inflammatory disorders.

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.

An improved method of treating cancers with engineered T cells is described.