44results about "Colony-stimulating factor" patented technology

The invention discloses a brain glioma animal model construction method based on an AAV mediated immune microenvironment. The method comprises the following steps: selecting an immunodeficient mouse at the right age; human CD34 + hematopoietic stem cells are injected for immune system reconstruction; human CD45 + immune cells in the peripheral blood PBMC are detected; the method comprises the following steps: selecting tumor tissues with high-expression brain glioma marker genes, carrying out rapid qPCR (quantitative polymerase chain reaction) or targeted RNA-seq immunohistochemical multiple verification, and screening consistent tumor tissues; the method comprises the following steps: physically dicing tumor tissues, treating the tumor tissues with pretreatment liquid, digesting the tumor tissues into single-cell suspension, and inoculating the single-cell suspension into a mouse cranium; an AAV vector carrying a specific immune regulation gene is injected into the tail vein of the mouse, and the brain glioma immune microenvironment is regulated; when it is observed that the tumor tissue grows stably and has immune cell infiltration characteristics, construction of the brain glioma animal model is completed. Compared with an existing model, the brain glioma model which is more stable, more scientific and closer to the human immune background is provided, and the brain glioma model is suitable for related immunotherapy drug screening and mechanism research.

The present invention provides a bifunctional molecule comprising an Fc mutant antibody linked to a cytokine, and the use of the bifunctional molecule in the manufacture of a therapeutic antibody drug. These Fc mutant monoclonal antibodies, monoclonal antibody / antigen complexes, or Fc fusion proteins can significantly reduce toxicity and side effects in vivo while maintaining the biological activity of the original antibody in vivo and in vivo.

This invention provides a side-chain coupled compound of a cell-binding molecule having a branched linker and an amanita toxin compound. [Solution] A side-chain conjugated compound of formula (I), TIFF2026097851000286.tif25170 In one embodiment, a side-chain conjugated compound is provided, in which T is a cell-binding agent / molecule, W is a C1-C18 extension unit, and D is an amanita toxin, or an isotope of a chemical element, or a pharmaceutically acceptable salt, hydrate, or hydrated salt; or a polymorphic crystal; or an optical isomer, racemate, diastereomer, or enantiomer thereof.

The invention relates to single chain polypeptides having IL-10 and CSF1 activities and to their use in therapy.

To provide a method for producing professional antigen-presenting cells, and to provide the professional antigen-presenting cells.SOLUTION: Provided are a method for producing professional antigen-presenting cells, including obtaining proliferative myeloid cells (pMC) by expressing c-MYC or the like in myeloid cells (MC) differentiated from pluripotent stem cells, and obtaining professional antigen-presenting cells (pAPC) by expressing GM-CSF and / or M-CSF in the pMC, and human professional antigen-presenting cells produced by the method.SELECTED DRAWING: None

A genetically-modified, immunodeficient mouse is provided along with methods of use, wherein the mouse includes (a) a nucleotide sequence encoding human stem cell factor (hSCF); (b) a nucleotide sequence encoding human granulocyte-macrophage colony-stimulating factor (hGM-CSF); (c) a nucleotide sequence encoding human interleukin-3 (hIL-3); and (d) a nucleotide sequence encoding human colony-stimulating factor 1 (hCSFl), wherein each of the nucleotide sequences is operably linked to a promoter, and wherein the genetically-modified, immunodeficient mouse expresses hSCF, hGM-CSF, hIL-3, and hCSFl, wherein the genetically-modified, immunodeficient mouse allows engraftment of human hematopoietic stem cells along with engraftment of human-patient derived tumor xenografts and / or human tumor cell lines to enable in vivo investigation of the interactions between the human immune system and human cancer.

The present application relates to immunomodulatory molecules comprising a first binding domain (e.g., an immunostimulatory cytokine, such as IL-2 or IL-12, or a variant thereof) that specifically recognizes a first target molecule (e.g., a receptor for an immunostimulatory cytokine) and a second binding domain (e.g., an agonist ligand, such as PD-L1 or PD-L2, or a variant thereof, or an agonist antigen-binding fragment, such as an anti-PD-1 agonist Fab, scFv, VHH, or full length antibody) that specifically recognizes a second target molecule (e.g., an inhibitory checkpoint molecule, such as PD-1), wherein the first binding domain, upon binding to the first target molecule, upregulates an immune response and the second binding domain, upon binding to the second target molecule, downregulates an immune response. Methods of making and using such immunomodulatory molecules are also provided.

The present invention discloses a method for constructing an animal model of glioma based on AAV-mediated immune microenvironment, comprising: selecting immunodeficient mice of appropriate age; injecting human CD34+ hematopoietic stem cells for immune system reconstruction; detecting human CD45+ immune cells in peripheral blood PBMC; selecting tumor tissues that highly express glioma marker genes, performing rapid qPCR or targeted RNA-seq immunohistochemistry multiple verification, and screening tumor tissues that meet the requirements; physically cutting the tumor tissue and treating it with a pretreatment solution, digesting it into a single cell suspension, and inoculating it into the mouse's skull; injecting an AAV vector carrying a specific immune regulatory gene into the mouse's tail vein to regulate the glioma immune microenvironment; when the tumor tissue is observed to grow stably and have immune cell infiltration characteristics, the construction of the glioma animal model is completed. Compared with existing models, the present invention provides a more stable, more scientific, and more human immune background glioma model, which is suitable for related immunotherapy drug screening and mechanism research.

The present invention is in the field of viral immunotherapy. The invention provides new pseudocowpox (PCPV) viruses, in particular recombinant PCPV, composition thereof as well as their therapeutic use for preventing or treating diseases, and, notably, proliferative diseases like cancers and restenosis and infectious diseases such as chronic ones. The present invention also provides methods for generating and amplifying such a PCPV and a method for eliciting or stimulating and / or re-orienting an immune response using such a PCPV. More specifically, the invention provides an alternative to the existing poxvirus vectors such as MVA (Modified Virus Ankara) and may be largely used for the therapeutic vaccination.

SOLUTION: Provided herein is a liquid formulation comprising recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) for inhalation by nebulization.SELECTED DRAWING: None

Provided is a method for producing professional antigen-presenting cells, said method comprising allowing myeloid cells (MC), which are differentiated from pluripotent stem cells, to express c-MYC, etc. to thereby give proliferating myeloid cells (pMC) and allowing the pMC to express GM-CSF and / or M-CSF to thereby give professional antigen-presenting cells (pAPC). Also provided are human professional antigen-presenting cells produced by this method.

Recombinant oncolytic viruses and their uses are provided. The recombinant oncolytic virus comprises an M protein and a cytokine encoded by a foreign gene. The M protein includes a mutation from methionine to arginine at position 51 (M51R), a mutation from valine to phenylalanine at position 221 (V221F), and a mutation from serine to arginine at position 226 (S226R) compared to the amino acid sequence shown in SEQ ID NO: 1. All of the provided recombinant oncolytic viruses have good infectivity and in vitro killing ability against abnormally proliferating (tumor) LLC cells, 4T1 cells, MC38 cells, and Hela cells, and are difficult to be removed within LLC cells, 4T1 cells, MC38 cells, and Hela cells, and the infectivity against normal cells is significantly reduced.

To provide a method for generating microglia from stem cells.SOLUTION: Disclosed is a method including the following steps of: a) targeted insertion of a nucleotide sequence encoding a transcriptional regulatory factor into a first safe harbor locus on a genome and b) targeted insertion of a coding sequence of a transcription factor PU.1 into a second safe harbor locus on the genome, in which the gene is functionally linked to an inducing promoter regulated by the transcriptional regulatory factor; and expression of PU.1 and culture of stem cells obtained from steps a) and b) while being exposed to a growth factor or a small molecule, the growth factor or the small molecule mimicking signal transduction during at least one stage from the embryonic development of microglia, or from the proliferation, differentiation, or polarization of adult-type microglia. Further, the present invention relates to microglia obtained by the method, and various applications thereof.SELECTED DRAWING: Figure 5A

A method for producing professional antigen-presenting cells and professional antigen-presenting cells are provided. [Solution] We provide a method for producing professional antigen-presenting cells, which includes obtaining proliferative myeloid cells (pMCs) by expressing c-MYC or the like in myeloid cells (MCs) differentiated from pluripotent stem cells, and obtaining professional antigen-presenting cells (pAPCs) by expressing GM-CSF and / or M-CSF in the pMCs, as well as human professional antigen-presenting cells produced by this method.

Genetically engineered progenitor cells and methods of using the same are disclosed herein. Genetically engineered cells differentiated from the genetically engineered progenitor cells of the present disclosure are also disclosed herein. Also disclosed herein is a method of treating a condition in a subject by administering the genetically engineered progenitor cells of the present disclosure or the genetically engineered cells differentiated from the genetically engineered progenitor cells.

Disclosed are single chain polypeptides exhibiting both Interleukin-10 (IL-10) and Colony-Stimulating Factor 1 (CSF1) activities. The polypeptides are engineered to selectively deliver the anti-inflammatory effects of IL-10 to myeloid cells that express the CSF1 receptor (CSF1R). In one embodiment, the polypeptide comprises a CSF1 monomer fused via a peptide linker to an IL-10 monomer. In another embodiment, the polypeptide comprises a single chain dimeric IL-10 fused to a CSF1 monomer. These fusion proteins provide targeted anti-inflammatory activity while reducing systemic effects on other immune cells. Pharmaceutical compositions containing these polypeptides and their use for treating inflammatory diseases, such as inflammatory bowel disease, are also provided.

This specification describes immunogenic compositions comprising tumor cells expressing a fusokine containing GM-CSF linked to IL-7 by a peptide linker. Also described are pharmaceutical compositions and methods for treating patients with glioblastoma using tumor cells expressing a fusokine containing GM-CSF linked to IL-7 by a peptide linker.

Genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein are provided. Also provided are genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein that have been engrafted with human cells such as human hematopoietic cells, and methods for making such engrafted mice. These mice find use in a number of applications, such as in modeling human immune disease and pathogen infection; in in vivo screens for agents that modulate hematopoietic cell development and / or activity, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to hematopoietic cells; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on hematopoietic cells; in in vivo screens of human hematopoietic cells from an individual to predict the responsiveness of an individual to a disease therapy, etc.

The disclosure provides, in various embodiments, non-human animals that comprise a human immune cell engraftment and / or functional human immune system. The disclosure also provides, in various embodiments, methods of generating said non-human animals. The disclosure also provides, in various embodiments, methods of determining immunogenicity of antigens or an immunogenic fragment thereof or antigenic therapies and / or identifying agents that modulate immune response.

A method of identifying anti-tumor activity of a test substance is provided along with a genetically-modified, immunodeficient mouse and methods of use, wherein the genetically-modified, immunodeficient mouse enables in vivo investigation of the interactions between the human immune system and human cancer.

A method of identifying anti-tumor activity of a test substance is provided along with a genetically-modified, immunodeficient mouse and methods of use, wherein the genetically-modified, immunodeficient mouse enables in vivo investigation of the interactions between the human immune system and human cancer.

An immunoresponsive cell, such as a T-cell expressing(i) a second generation chimeric antigen receptor comprising:(a) a signalling region;(b) a co-stimulatory signalling region;(c) a transmembrane domain; and(d) a binding element that specifically interacts with a first epitope on a target antigen; and(ii) a chimeric costimulatory receptor comprising(e) a co-stimulatory signalling region which is different to that of (b);(f) a transmembrane domain; andg) a binding element that specifically interacts with a second epitope on a target antigen.This arrangement is referred to as parallel chimeric activating receptors (pCAR). Cells of this type are useful in therapy, and kits and methods for using them as well as methods for preparing them are described and claimed.

In various embodiments, the present disclosure provides non-human animals comprising human immune cell transplantation and / or a functional human immune system. In various embodiments, the disclosure also provides methods of making the non-human animal. In various embodiments, the disclosure also provides methods of determining the immunogenicity of an antigen or an immunogenic fragment thereof or an antigen therapy and / or identifying an agent that modulates an immune response.

Genetically engineered progenitor cells and methods of using the same are disclosed herein. Genetically engineered cells differentiated from the genetically engineered progenitor cells of the present disclosure are also disclosed herein. Also disclosed herein is a method of treating a condition in a subject by administering the genetically engineered progenitor cells of the present disclosure or the genetically engineered cells differentiated from the genetically engineered progenitor cells.

Compositions and methods for modifying granulocyte-macrophage colony-stimulating factor (GM-CSF) as described. Non-naturally occurring cell engineered for production of GM-CSF with an altered glycosylation pattern comprising an expression vector having the CSF2 gene, and one or more knockout genes selected from the group consisting of MGAT5, ST3GAL3, ST3GAL4, ST3GAL6, B3GNT2, SPPL3, MGAT4A, and MGAT4B. In some embodiments, the cell additionally comprises a knock-in gene consisting of HST6GAL1.

The present invention provides: an oncolytic virus such as a conditionally replicating adenovirus carrying the CXCL10 gene; the oncolytic virus additionally carrying the IL-2 gene and / or the GM-CSF gene on the same viral genome; a combination of the oncolytic virus and a separate oncolytic virus carrying the IL-2 gene and / or the GM-CSF gene; and a cancer treatment agent comprising any of the aforementioned oncolytic viruses or a combination thereof as an active ingredient.