1544results 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.

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.

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.

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 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.

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 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.

The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (IL15) payloads, as well as compositions and methods of use thereof.

Provided herein are IL- 18 polypeptide prodrugs comprising IL- 18, a half-life extension element, an IL- 18 blocking element and a protease cleavable linker. Also provided herein are pharmacal compositions thereof, as well as nucleic acids, recombinant expression vectors, host cells for making such polypeptide prodrugs. Also disclosed are methods of using the polypeptide prodrugs in the treatment of diseases, conditions and disorders.

A recombinant interleukin-27 (IL27) expressing virus is described. The recombinant IL27 expressing virus comprises an oncolytic virus comprising one or more exogenous nucleic acid sequences capable of expressing in IL27 protein or a biologically active portion thereof, the exogenous nucleic acid sequences being operably linked to an expression control sequence. Methods of treating cancer by in a subject by contacting a cancer cell of the subject with a recombinant IL27 expressing virus are also described.

The present invention relates to a fusion protein comprising an antibody against T cell surface molecule, interleukin-2 and a Fc region of an immunoglobulin. The fusion protein is a heterodimer or homodimer. The present invention also relates to use of the fusion protein in the manufacture of an anti-tumor drug.

Provided herein are compositions of NK-92™ cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.

The invention provides a construction method and application of a gene modified K562 cell line, and belongs to the technical field of biological medicines. According to the invention, two viruses CD86-4-1BBL and mbIL-21 are respectively subjected to gene transduction packaging by adopting a third-generation lentivirus four-plasmid packaging system, a K562 cell line is infected by the lentiviruses CD86-4-1BBL and mbIL-21, and a monoclonal cell line capable of stably expressing CD86, 4-1BBL and mbIL-21 proteins is obtained through screening. According to the method, cell lines with the cloning numbers of V5-E9, V10-A5, V5-D6 and V6-D7 are obtained through screening, the four cloning cell lines can serve as feeder cells for stimulating NK cell amplification after being amplified and subjected to irradiation treatment, NK cell amplification can be effectively promoted, the amplification multiple of the NK cells reaches up to 6000-8000, and large-scale preparation and production of the NK cells for treatment are met.

The invention provides novel fusion proteins of Interleukin 15 and prodrugs, and compositions and methods of preparation thereof, useful in treating various diseases and disorders (e.g., hyperplasia, solid tumor or hematopoietic malignancy).

Provided are methods of treating liver diseases comprising administering recombinant proteins comprising an interleukin-18-binding protein and an antigen binding fragment that binds to serum albumin.

Embodiments are described that relate to methods and systems for expanding cells in hollow fiber bioreactors. In embodiments, the cells are exposed to multiple growth factors, including combinations of recombinant growth factors. In other embodiments, the cells are grown in co-culture with other cells, e.g., hMSCs. In embodiments, the cells comprise CD34+ cells. The coated membrane comprises a membrane having a first coating configured to promote cell attachment to the membrane and a second coating comprising a soluble protein moiety.

Provided herein are transmembrane proteins containing a cytokine or a functional portion thereof, such as an interleukin or a functional portion thereof. In some aspects, the disclosure further relates to engineered cells and compositions comprising the transmembrane proteins and methods for their administration to subjects. In some embodiments, the cells engineered to contain the transmembrane protein, such as immune cells, further contain a genetically engineered recombinant receptor, such as a chimeric antigen receptor (CAR). In some embodiments, features of the transmembrane proteins, engineered cells, and methods and uses thereof provide for improved treatment of diseases or disorders.

Provided herein are compositions of NK-92™ cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.