3863results about "Genetically modified cells" patented technology

The invention discloses a novel application of an RNF6 gene, namely, an application of screening a medicine for preventing and / or treating Zika virus infection, aiming at inhibiting expression of the RNF6 gene or knocking out the RNF6 gene. A series of functional experiments prove that the RNF6 gene promotes the replication of the Zika virus, and the purpose of reducing the replication of the Zika virus can be achieved by using an expression inhibitor of the RNF6 gene or knocking out the RNF6 gene; experimental results show that the RNF6 gene can be used as a potential target for preventing and / or treating Zika virus infection, and a new direction is provided for development of drugs for preventing and / or treating Zika virus infection targeting the RNF6 gene in the future.

Disclosed are compositions and methods for preventing graft versus host disease (GVHD) in subjects receiving donor cells. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer suppress alloreactive donor cells. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

The invention discloses an anti-TP53 mutation T cell receptor and application thereof, the T cell receptor comprises specific alpha chain and beta chain variable domains, and the complementary determining region (CDR) sequence is shown as SEQ ID NO: 9-14. The TCR has the core advantage that the TCR has excellent broad-spectrum recognition capability, can target six different amino acid substitutions (A, G, I, N, S and T) at the R249 site, and effectively deals with tumor heterogeneity and mutation difference between patients. Aiming at high-frequency HLA-B * 07: 02 alleles in people, the TCR lays a foundation for developing TCR-T cell therapy covering a wide range of people, and has great clinical application value and market potential in treatment of various solid tumors carrying TP53 R249 hotspot mutation, such as liver cancer.

Provided are a fusion protein (for example, in the form of a bispecific antibody) binding to CD235a and CD3, a preparation method therefor, and a related use thereof.

Provided herein are engineered immune cells and populations thereof for administration to patients to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) to target tumor cells or other damaged cells in the patient and / or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

Provided herein are chimeric cytokine receptors bearing a binding domain capable of binding a TGF-β ligand or a TGF-β receptor antibody. When present on chimeric antigen receptor (CAR)-bearing immune cells (CAR-T-cells), such receptors allow for increased CAR-T cell expansion, activity and persistence, constitutively and / or through engagement of a TGF-β ligand or a TGF-β receptor antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.

The present invention relates to a modified stem cell and an ex vivo method for preparing defined mature cells from genetic programming of said modified stem cell which can be carried out in absence of certain growth factors, as well as a kit allowing to transform stem cells, and the different uses of the mature cells, for example for in vitro drug screening and toxicology or as cultivated meat. The genetic programming involves a molecular switch between two mutually exclusive programs of stem cell expansion and differentiation. The invention may be used for stem cells or other progenitors cells of any type, from any eukaryotic organism, but finds particular application in pluripotent stem cells from humans and livestock animals.

The invention belongs to the technical field of biological medicine, and particularly relates to an engineered cell microvesicle and a delivery system based on the engineered cell microvesicle, the system realizes efficient preparation of 1-5 [mu] m cell microvesicles, and the cell microvesicles have a large space volume and can be used for preparing the cell microvesicles. The carrier can be used for loading and delivery of target protein, polypeptide and recombinase which are specifically expressed in mother cells. The system transfects mother cells through lentivirus transfection or plasmid transfection to further produce cell microvesicles, and the microvesicles can load more goods and inherit membrane proteins of the mother cells, and can also effectively load intracellular proteins to realize effective delivery. By virtue of good structural stability, high immunogenicity and excellent biocompatibility, the cell microvesicle reduces systematic toxic and side effects of a traditional carrier, is expected to become an effective drug delivery system, and has great application potential in the field of gene therapy.

Genetically engineered immune cells, which express at least two metabolism modulating polypeptides and optionally a chimeric receptor polypeptide (e.g., an antibody-coupled T cell receptor (ACTR) polypeptide or a chimeric antigen receptor (CAR) polypeptide) capable of binding to a target antigen of interest. Also disclosed herein are uses of the engineered immune cells for inhibiting cells expressing a target antigen in a subject in need thereof.

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.

A chimeric autoantibody receptor (CAAR) that enables targeting of an immune cell to autoantibody producing B cells. The CAAR includes an autoantigen or fragment thereof that is bound by autoantibodies associated with neurological autoimmune disease primarily targeting the central nervous system. Also disclosed is a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), the nucleic acid sequence encoding an autoantigen or fragment thereof that is bound by autoantibodies associated with a neurological autoimmune disease primarily targeting the central nervous system, a transmembrane domain, and an intracellular signaling domain, a vector comprising a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), a genetically modified immune cell comprising the nucleic acid molecule encoding the CAAR and use of the immune cell in the treatment or prevention of a neurological autoimmune disease primarily targeting the central nervous system, such as an autoimmune encephalopathy or encephalomyelopathy, preferably anti-NMDAR encephalitis.

Disclosed herein are universal donor stem cells and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming the immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor stem cells disclosed herein do not express one or more MHC-I and MHC-II human leukocyte antigens. Similarly, in certain embodiments, the universal donor stem cells disclosed herein do not express one or more human leukocyte antigens (e.g., HLA-A, HLA-B and / or HLA-C) corresponding to MHC-I and MHC-II human leukocyte antigens, thereby rendering such cells hypoimmunogenic.

Embodiments provided herein include methods and compositions comprising anti-dinitrophenol chimeric antigen receptors (CARs). Some embodiments include nucleic acids encoding such CARs, polypeptides encoded by such nucleic acids, cells comprising such nucleic acids or polypeptides, and methods utilizing such cells. Some embodiments also include the use of dinitrophenol (DNP) and derivatives thereof.

Provided herein is a recombinant protein comprising a transmembrane domain derived from a transmembrane domain of a wild type erythropoietin receptor (EPOR). Nucleic acid molecules encoding such recombinant proteins, recombinant constructs, vectors and cells containing the nucleic acid molecules, methods of producing such cells and therapeutic uses thereof are also provided.

Methods for differentiating pluripotent stem cells to neuroectoderm in dynamic suspension culture using small molecule or protein inhibitors of TGFβ / Activin / Nodal signaling and BMP signaling are provided. Also provided are methoc and protocols for differentiating pluripotent stem cells such as human embryonic stem cells first to neuroectoderm, then further to glial progenitor cells, and further to oligodendrocyte progenitor cells (OPCs), and compositions obtained thereby. The methods of the present disclosure reproducibly produce neuroectoderm progenitor cells by day 7 of the differentiation process, glial progenitor cells by day 21 of the differentiation process and OPCs by day 42 of the differentiation process.

Provided herein are methods and related compositions for enhancing or enhanced partial reprogramming of target cells in a subject in need thereof (e.g., a human subject suffering from or at risk of a disease), the method comprising administering a plurality of mesenchymal lineage progenitor or stem cells (MLPSCs), exosomes derived therefrom, or conditioned culture media derived therefrom to a subject that expresses or will express one or more reprogramming factors in a population of target cells, whereby a plurality of the target cells in the subject become partially reprogrammed, but not fully reprogrammed.

The present invention relates to: a receptor tyrosine kinase like orphan receptor 1 (ROR 1) antibody or an antigen-binding fragment thereof; a nucleic acid encoding same; a recombinant expression vector carrying the nucleic acid; a host cell transinfected with the recombinant expression vector; a method for preparing the antibody or the antigen-binding fragment thereof; a bi- or multi-specific antibody bearing the antibody or the antigen-binding fragment thereof; an immune cell-engaging bi- or multi-specific antibody; an antibody-drug conjugate (ADC) in which the antibody or the antigen-binding fragment thereof is bound to a drug; a chimeric antigen receptor (CAR) containing the scFv of the antibody as an antigen-binding site of an extracellular domain; an immune cell having the chimeric antigen receptor introduced thereinto; a composition for combination therapy including the antibody or the antigen-binding fragment thereof; a composition for preventing or treating cancer; and a method for preventing or treating cancer.

The invention discloses a bipeptide modified bionic nano-vesicle as well as a preparation method and application thereof, and belongs to the field of biological medicines. The dipeptide modified bionic nano-vesicle comprises nano-particles formed by PLGA (poly (lactic-co-glycolic acid)), and the nano-particles are loaded with a medicine with a nerve protection or nerve repair effect; the surface of the nanoparticle is coated with a macrophage membrane for expressing RVG peptide and T7 peptide. The bipeptide modified bionic nano-vesicle simultaneously presents T7 peptide and RVG peptide through an engineered macrophage membrane, the T7 peptide is combined with a blood-brain barrier transferrin receptor through high affinity to realize efficient brain entry, astrocytes in the brain are specifically recognized by virtue of the RVG peptide, accurate recognition and delivery of target cells in a focus area are realized, and the bipeptide modified bionic nano-vesicle has a good application prospect. Meanwhile, the natural inflammation tropism and immune escape ability of a macrophage membrane are reserved, and the problems that a traditional drug delivery system is low in targeting precision, and cross-barrier distribution and intracerebral distribution are difficult to cooperate are solved.

Provided herein are compositions, methods, and uses involving anti-Mucin-16 (MUC16) agents that immunospecifically bind an epitope of Mucin-16 (MUC16). Also provided herein are uses and methods for managing, treating, or preventing disorders, such as cancer and diseases associated with positive MUC16 expression.

The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

The invention relates to an STING gene knockout TIL capable of enhancing anti-tumor activity and a preparation method and application of the TIL, in particular to a genetically engineered immune cell, and an STING gene in the genetically engineered immune cell is silenced or down-regulated. The ferroptosis resistance of the immune cell provided by the invention is remarkably enhanced, the immune cell can be better infiltrated into a tumor microenvironment, and the immune cell has a remarkable anti-tumor effect.

The application relates to the field of biotechnology, in particular to a Faecalibacterium prausnitzii microbial anti-inflammatory molecule and a screening method and application thereof. The amino acid sequence of the Faecalibacterium prausnitzii microbial anti-inflammatory molecule is shown in (a) or (b); (a) the amino acid sequence is shown in SEQ ID NO. 1; (b) a protein derived from (a) with anti-inflammatory activity obtained by substituting, deleting or adding one or more amino acids in the amino acid sequence in (a). Compared with the microbial anti-inflammatory molecule protein of a representative strain A2-165 of the Faecalibacterium genus, the inhibiting effects of the Faecalibacterium prausnitzii microbial anti-inflammatory molecule on the NF-kappa B signal pathway and the inflammatory factor TNF alpha are 50% and 56% respectively, and the anti-inflammatory effect (inhibiting the NF-kappa B signal pathway) of the Faecalibacterium prausnitzii microbial anti-inflammatory molecule screened in the application can reach more than 90%, and the Faecalibacterium prausnitzii microbial anti-inflammatory molecule has the advantages of small use dosage and strong anti-inflammatory effect.

The present disclosure is directed recombinant T cell receptors capable of binding a gp100 epitope and nucleic acid molecules encoding the same. In some embodiments, the nucleic acid molecules further comprise a second nucleotide sequence, wherein the second nucleotide sequence or the polypeptide encoded by the second nucleotide sequence inhibits the expression of an endogenous TCR. Other aspects of the disclosure are directed to vectors comprising the nucleic acid molecule and cells comprising the recombinant TCR, the nucleic acid molecule, or the vector. Still other aspects of the disclosure are directed to methods of using the same. In some embodiments, the methods comprise treating a cancer in a subject in need thereof.

The invention belongs to the field of veterinary biological products, and particularly relates to a chicken infectious laryngotracheitis recombinant subunit vaccine as well as a preparation method and application thereof. A core antigen of the vaccine is a recombinant gB trimer glycoprotein (gB-Trimer) modified by genetic engineering, and the protein successfully locks a prefusion conformation with the strongest immunogenicity of the gB protein through strategies of truncation, trimerization motif splicing, dual-stability mutation and the like. The vaccine prepared by the invention can stimulate rapid and lasting neutralizing antibody response, provide 100% clinical protection and effectively block replication and detoxification of the ILTV, has extremely high biological safety compared with a traditional live vaccine, completely eliminates risks of poison dispersion and enhancement, and provides a safe and efficient novel solution for prevention and control of the ILTV.

Disclosed are an antigen-binding protein, a multispecific antibody, a nucleic acid encoding an antigen-binding protein or a multispecific antibody, a vector comprising the nucleic acid, a cell comprising an antigen-binding protein, a multispecific antibody, a nucleic acid or a vector, and a method for preparing a cell. Further disclosed are a conjugate or composition comprising an antigen-binding protein or a multispecific antibody, a method for preventing and / or treating a disorder by using an antigen-binding protein, a multispecific antibody or a cell, and a method for detecting the presence of a disorder in a subject.

The present disclosure features modified immune effector cells (e.g., T cells or NK cells) having increased resistance to inhibition of an immunosuppressive agent relative to unmodified immune effector cells, compositions comprising the same, and methods of using the same.

Provided herein are chimeric antigen receptors (CARs) for cancer therapy, and more particularly, CARs containing a scFv from a CD33 monoclonal antibody. Provided are immune effector cells containing such CARs, and methods of treating proliferative disorders such as acute myeloid leukemia (AML), and relapsed or refractory AML.

Systems and methods are presented that provide for improved NK cell function. In preferred aspects, NK-92 cells express recombinant er / LSP-IL-15 to so render the NK-92 cells independent of exogenous cytokines and to provide extracellular immune stimulation.