149 results about "Host disease" patented technology

The purpose of the present invention is to provide: a novel therapeutic or prophylactic agent for xerophthalmia; a therapeutic or prophylactic agent for graft-versus-host disease; a corneal epithelium wound healing promoter; a corneal invasive inflammatory cell inhibitor; or an inhibitor of differentiation of lymphocytes into effector T cells. The present invention provides: a therapeutic or prophylactic agent for xerophthalmia, a therapeutic or prophylactic agent for graft-versus-host disease, a corneal epithelial wound healing promoter, a corneal invasive inflammatory cell inhibitor, a tear amount maintenance agent, a corneal epithelial damage inhibitor, and a method for preparing the same, which comprises, as an active ingredient, a substance derived from a stem cell culture supernatant; a cell proliferation marker positive cell inhibitor, or an inhibitor of differentiation of lymphocytes to effector T cells.

The invention provides sgRNA for targeting and guiding nuclease to efficiently cut an HLA-DRA gene, a method for modifying a CAR-T cell by using the sgRNA, and a related gene editing system, reagent and kit. According to the CAR-T cell, the immunogenicity is greatly reduced, the risk of graft versus host disease and immunological rejection can be effectively reduced, and meanwhile the killing capacity of tumor cells of the CAR-T cell is not affected.

The present invention relates to high density lipoprotein (HDL) or HDL mimetics for use in the prevention and / or treatment of graft-versus-host disease (GvHD) or cytokine release syndrome in a subject.

The invention relates to bispecific antibodies comprising a first antigen-binding domain that specifically binds to TfR and a second, and optionally a third, antigen-binding domain that specifically binds to PD1. The invention further relates to methods of producing these molecules, to methods of using the same, to pharmaceutical compositions thereof, and their use as medicaments for the treatment of cancer, of acute and chronic infections and of Graft-versus-host disease.

This invention provides an antibody composition with improved stability, exhibiting reduced fragmentation of the antibody polypeptide chain during manufacturing and subsequent storage. [Solution] This disclosure relates to improved compositions and methods for treating T cell-mediated diseases and disorders (e.g., autoimmune disorders, graft-versus-host diseases, and graft rejection). Provided are antibody-containing anti-αβTCR binding polypeptides comprising at least one amino acid substitution or modification that enhances the stability of the binding polypeptide by reducing fragmentation of the light chain variable region. Methods provided herein generally involve administering an effective amount of a stabilized, humanized binding polypeptide specific to the alpha-beta T cell receptor (αβTCR) to a subject in need thereof.

The present application relates to interleukin-2 variants and methods of use thereof. The present invention relates to polypeptides that share a primary sequence with human IL-2 in addition to several mutated amino acids. A panel of IL-2 variants comprises mutations with profound impressive manufacturability that preferentially promote proliferation, survival, activation and / or function of immunosuppressive regulatory T cells (Treg: CD4 + CD25 + FoxP3 +) over effector T cells and NK cells. Also included is the therapeutic use of such IL-2 selective agents, alone or in combination with immunomodulators or disease tissue targeting antibodies, proteins or peptides, for the treatment of Treg cell deficiency, various autoimmune and inflammatory disorders, organ transplantation and graft versus host disease. In another aspect, the invention relates to pharmaceutical compositions comprising the disclosed polypeptides. Finally, the invention relates to the therapeutic use of the disclosed polypeptides and pharmaceutical compositions due to their selective modulation of the immune system on diseases such as autoimmune and inflammatory disorders.

This disclosure relates to an immunoglobulin single variable domain (ISVD)-containing modulator that allosterically binds to a three-dimensional (3D) epitope of a protein complex comprising at least one inhibitory immune receptor and at least one corresponding ligand. The modulator regulates cooperativity within such complexes, thereby affecting the binding affinity and downstream signaling pathways. Specifically, the allosteric modulator of this invention induces positive cooperativity in immunoinhibitory receptor-ligand complexes, thus suppressing immune responses in a spatiotemporally restricted manner. Accordingly, these allosteric modulators are useful as therapeutic agents for inflammatory diseases, such as autoimmune diseases, allergic diseases, or graft-versus-host disease (GVHD). Moreover, this disclosure pertains to methods for identifying, selecting, and producing said allosteric modulators.

The present invention provides a method of reducing the likelihood of a subject having graft versus host disease or a method of treating graft versus host disease in a subject comprising analyzing a gastrointestinal biopsy of the subject to measure the number and density proportion of cells and administering to the subject a pharmaceutically effective amount of one or more immunosuppressive agents.

The present invention provides a prophylactic or therapeutic composition for graft-versus-host disease (GVHD). There is provided a prophylactic or therapeutic composition for GVHD, which comprises bacteria belonging to any genus selected from the group consisting of the following genera: Blautia, Clostridium, unclassified Clostridiales, Actinomyces, Parabacteroides, Lachnoclostridium, Bacteroides, Faecalibacterium, unclassified Lachnospiraceae, Roseburia, Ruminococcus, unclassified Firmicutes, Dorea, Phascolarctobacterium, Sutterella, Megamonas, Collinsella, Eubacterium, and Coprococcus, etc., or any combination of bacteria belonging to these genera.

The present invention provides a liposome preparation containing a population of liposomes containing a CD1d ligand compound, wherein the average particle size of the population of liposomes is 90 to 110 nm and the polydispersity index of particle size distribution is 0.2 or less. and the polydispersity index of the particle size distribution is 0.2 or less. The present invention also provides the use of the liposome preparation in the prevention or treatment of graft-versus-host disease and organ transplant rejection.

The application discloses a method for establishing a mouse model of MHC haplotype compatible allogeneic hematopoietic cell transplantation, and belongs to the technical field of animal experiment model construction. The technical problem to be solved by the application is how to construct a mouse model which can be used to study the immune reconstruction mechanism and treatment effect evaluation of MHC haplotype compatibility and MHC full compatibility in bone marrow cell transplantation recipient mice. To solve the technical problem, the application provides a method for constructing a mouse model of MHC haplotype compatible allogeneic hematopoietic cell transplantation, which comprises transplanting bone marrow cells of a donor mouse into a recipient mouse, and the MHC haplotype of the donor mouse and the recipient mouse is compatible. The application sets a modeling condition, and the model establishment condition is evaluated by survival condition, graft-versus-host disease and rejection reaction observation, flow cytometry and histopathological section, so as to prove that the model is reliable and stable.

The present invention provides a novel use and methods comprising antibodies, or antigen-binding fragments thereof, which bind to a CCR7 receptor for use as a novel therapeutic agent in prevention and / or treatment of graft versus host disease (GVHD), preferably in hematopoietic stem cell transplantation (HSCT), more preferably allogeneic hematopoietic stem cell transplantation. GVHD of the invention can be acute (aGVHD) and / or chronic (cGVHD), preferably acute. The antibodies and antigen-binding fragments are capable of selectively depleting ex vivo or in vitro immune cells expressing CCR7 and are capable in vivo of selectively killing immune cells expressing a CCR7 receptor and of impairing / blocking migration and of activation of said immune cells, which are involved in the development and evolution of GVHD. The use of said antibodies for depleting, killing and impairing / blocking migration and activation of immune cells expressing CCR7 cells is disclosed, thus providing an alternative therapy for preventing and treating GVHD in both acute and chronic types.

This invention relates to double-stranded oligonucleotides complementary to JAK1 that result in the regulation of JAK1 expression. Regulation of JAK1 expression is beneficial for a range of medical disorders, including inflammatory bowel disease, organ transplant rejection, graft-versus-host disease, multiple sclerosis, rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriasis, dermatitis, diabetic nephropathy, systemic lupus erythematosus (SLE), dry eye disease, cancer, myelofibrosis, and asthma. The invention also includes compositions comprising double-stranded oligonucleotides and therapeutic methods using double-stranded oligonucleotides.

The present invention relates to a compound of Formula (I), in particular, the compound of Formula (II) or an isotopic variant, a pharmaceutically acceptable salt or solvate thereof for use in a method of treatment of graft-versus-host disease in a subject in need thereof.

The present application belongs to the field of photochemical therapy, and particularly relates to a method for photochemical treatment of riboflavin based on multi-wavelength LED and application thereof in treatment of graft-versus-host disease. The present application selects different wavelength LED combinations as light sources to optimize the riboflavin photochemical method, controls the light intensity at 1000-25000 μW / cm², controls the irradiation time at 5-15 minutes, and controls the riboflavin concentration at 20-150 μM, thereby significantly improving the photochemical reaction effect. The method can efficiently induce PBMC apoptosis in a plasma environment, significantly reduces the levels of key pro-inflammatory cytokines such as TNF-α, IL-6 and IFN-γ, and has no significant influence on platelets, hemoglobin and blood clotting function, thereby providing a safe and controllable new cell preparation method for GVHD treatment.

A method for treating subjects with graft-versus-host disease (GvHD) or at risk of developing GvHD, using CD90 with stronger immunomodulatory capabilities. + hAEC cell populations were used as the primary therapeutic cells. Studies on the related mechanism of action revealed that CD90... + hAECs showed significantly higher levels of stem cell pluripotency markers SSEA4, OCT4, and NANOG than typical hAECs, and also exhibited better immunomodulatory functions; therefore, CD90 was used as a marker. + hAECs cells can be used as a treatment to achieve better clinical outcomes.

To provide a novel cell therapeutic agent that can improve GVHD treatment efficacy by strengthening immunomodulatory activity of MSC through use of a TLR5 agonist.SOLUTION: The present invention relates to a pharmaceutical composition for prevention or treatment of graft-versus-host disease, the composition containing, as an active ingredient, mesenchymal stem cells treated with a TLR5 (Toll-like receptor 5) agonist. The composition of the present invention is excellent in ability to reduce variability under a low-grade inflammatory environment and to exert an immunomodulatory effect, and can be utilized as an MSC-based therapeutic agent for steroid-resistant graft-versus-host disease (GVHD).SELECTED DRAWING: Figure 5b

The invention belongs to the technical field of medicines, and particularly relates to a 4, 5, 6, 7-tetrahydropyrazolo [1, 5-a] pyrazine derivative and application thereof. The derivative disclosed by the invention is a compound shown in a general formula (I) and pharmaceutically acceptable salts thereof, and A, L and Q are described in the specification. The compound disclosed by the invention has relatively strong ROCK2 inhibitory activity in vitro, and can be used for treating ROCK2 related diseases, such as chronic graft versus host disease, tumor or fibrosis and the like.

The invention discloses a construction method of an acute graft-versus-host disease model after hematopoietic stem cell transplantation based on intestinal organs, relates to the technical field of biology, and is technically characterized in that the invention provides the construction method of the acute graft-versus-host disease model after hematopoietic stem cell transplantation based on the intestinal organs. T cells can exert the chemotactic ability and recognition function, and the model provides a new thought for studying the disease progress and treatment means of intestinal aGVHD.

The invention relates to the technical field of cell engineering, in particular to a preparation method of immune regulation type stem cells for treating graft versus host diseases. The invention provides a preparation method of immune regulation type stem cells for treating graft versus host diseases, which comprises the following steps: (1) cleaning a human fat aspirator, and digesting with collagenase to obtain mononuclear cells; (2) inoculating the mononuclear cells obtained in the step (1) into a differential culture medium, culturing for 2-3 days, and further culturing the adherent cells for 18-22 days to obtain mesenchymal stem cells; and (3) inoculating the mesenchymal stem cells obtained in the step (2) into an induction culture medium for induction culture, and screening to obtain the immune regulation type stem cells. According to the preparation method provided by the invention, the technical problems of unstable source, function attenuation and poor treatment effect of the immune regulation type stem cells in the prior art are solved, and an efficient, safe and standardized new scheme is provided for treatment of GVHD.

The present disclosure relates to extracellular vesicles (EVs), e.g., exosomes, comprising a payload (e.g., an antigen, adjuvant, and / or immune modulator) and / or a targeting moiety. Also provided herein are methods for producing the EVs (e.g., exosomes) and methods for using the EVs (e.g., exosomes) to treat and / or prevent diseases or disorders, e.g., cancer, graft-versus-host disease (GvHD), autoimmune disease, infectious diseases, or fibrotic diseases.

This invention relates to the selective removal of activated T cells using a monovalent antibody or its antigen-binding fragment, which includes heavy chain variable regions and light chain variable regions of an antibody that specifically binds to CD3. In one embodiment of the present invention, the monovalent anti-CD3 antibody or its antigen-binding fragment is useful as a T cell removal agent or T cell immunosuppressant because it can selectively remove only activated T cells without affecting non-activated T cells. In particular, this invention is useful for the prevention or treatment of T cell-mediated autoimmune diseases, graft-versus-host diseases, or organ transplant rejection, as well as for the prevention of graft-versus-host disease (GVHD) side effects in allogeneic CAR-T cell therapy.

The present invention is related to human platelet lysate or a fraction that is enriched for human platelet lysate derived extracellular vesicles and their use in medicine, particularly for the prevention and / or treatment of inflammatory driven diseases, neurodegenerative diseases, immune / autoimmune diseases, cardiovascular diseases, dermatologic diseases, orthopedic diseases, tissue regenerative medicine, oncologic diseases, infectious diseases, transplant rejections, stroke, ischemia or Graft-versus-Host Disease. The present invention is further related to a method of manufacture of a pharmaceutical preparation or a diagnostic preparation or a cosmetic preparation comprising the step of adding human platelet lysate or a fraction that is enriched for human platelet lysate derived extracellular vesicles to the pharmaceutical preparation or a diagnostic preparation or a cosmetic preparation.

To provide compositions comprising components of multi-component CALs or CARs, and to provide methods for treating autoimmune diseases and the like.SOLUTION: A composition is provided comprising a TCR recognition domain and one or both of (a) an intracellular signaling domain and (b) a first-type protein interaction domain. Further provided is a method for treating or preventing autoimmune disease, transplant rejection, or graft-versus-host disease.SELECTED DRAWING: Figure 10

The anti-CD40L / anti-CD28 bispecific antibody according to the present application comprises anti-CD40L scFv and anti-CD28 scFv, and thus does not exhibit a thromboembolic side effect, can exhibit an excellent effect of treating autoimmune diseases and / or graft versus host diseases while preventing a T cell activation effect caused by CD28 dimer formation, and can be used as a novel anti-CD40L / anti-CD28 bispecific antibody. In addition, excellent bispecific antibody physical characteristics can be shown.

The invention particularly discloses application of TGM2 in preparation of a medicine for treating allogenic hematopoietic stem cell transplantation complications, and relates to the technical field of biological medicine. According to the invention, the application of the overexpressed TGM2 extracellular vesicles in preparation of drugs for treating acute infection and graft versus host disease is provided for the first time, human HEK293T cells are transfected through a TGM2 overexpressed lentiviral vector, and the overexpressed TGM2 extracellular vesicles are obtained after screening, culture, separation and purification. Animal model experiments prove that the overexpressed TGM2 extracellular vesicles effectively relieve clinical symptoms of mice with acute graft-versus-host diseases, prolong the life cycle of the mice and have good clinical transformation and clinical application prospects.

This disclosure relates to extracellular vesicles (EVs), such as exosomes, comprising a payload (e.g., an antigen, adjuvant, and / or immunomodulator) and / or a targeting portion. Methods for generating EVs (e.g., exosomes) and methods for using EVs (e.g., exosomes) to treat and / or prevent diseases or conditions, such as cancer, graft-versus-host disease (GvHD), autoimmune diseases, infectious diseases, or fibrotic diseases, are also provided herein.

The present invention relates to the prophylactic or therapeutic use of GLP-2 derivatives and / or long-acting conjugates thereof for graft versus host disease. In addition, the present invention relates to the prophylactic or therapeutic use of a GLP-2 derivative and / or a long-acting conjugate thereof in combination with a steroid for steroid refractory graft versus host disease.

The present invention relates to anti-human BTLA agonist antibodies and their use for the prevention or treatment of inflammatory or autoimmune diseases or disorders such as systemic lupus erythematosus or graft versus host disease.

The invention discloses a bicyclic compound and an application of the bicyclic compound in a medicine, and particularly relates to a novel bicyclic compound and a medicine composition containing the novel bicyclic compound. The invention also relates to a method for preparing the compound, and application of the compound or the pharmaceutical composition in preparation of drugs for treating RIPK1 inhibitor mediated diseases and / or symptoms. The invention relates to the field of medicines, in particular to the application of the medicines in preparing medicines for treating diseases such as idiopathic pulmonary fibrosis, graft versus host disease, ulcerative colitis, rheumatoid arthritis, multiple sclerosis, amyotrophic lateral sclerosis, systemic inflammatory response syndrome, lupus erythematosus, Alzheimer's disease, psoriasis, non-alcoholic steatohepatitis, osteoarthritis and the like.